KEGG   PATHWAY: umr04623
Entry
umr04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Ursus maritimus (polar bear)
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
umr04623  Cytosolic DNA-sensing pathway
umr04623

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656671  GSDMD; gasdermin-D isoform X2 [KO:K20917]
103656833  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
103657131  IRF3; interferon regulatory factor 3 [KO:K05411]
103657312  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
103657480  CGAS; cyclic GMP-AMP synthase isoform X1 [KO:K17834] [EC:2.7.7.86]
103657888  [KO:K12799]
103658871  IL6; interleukin-6 [KO:K05405]
103658896  GSDME; gasdermin-E [KO:K22146]
103658916  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103659742  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
103661015  NFKBIB; LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta [KO:K02581]
103661503  POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 isoform X1 [KO:K03009]
103662147  [KO:K05414]
103662148  [KO:K05414]
103662149  [KO:K05414]
103662150  IFNB1; interferon beta [KO:K05415]
103662207  IL33; interleukin-33 isoform X1 [KO:K12967]
103662382  IL18; interleukin-18 [KO:K05482]
103663110  DNASE2B; deoxyribonuclease-2-beta [KO:K01158] [EC:3.1.22.1]
103663769  STING1; stimulator of interferon genes protein isoform X2 [KO:K12654]
103664063  POLR1C; DNA-directed RNA polymerases I and III subunit RPAC1 isoform X1 [KO:K03027]
103664404  POLR1D; DNA-directed RNA polymerases I and III subunit RPAC2 [KO:K03020]
103664437  DDX41; probable ATP-dependent RNA helicase DDX41 isoform X1 [KO:K13116] [EC:3.6.4.13]
103664573  G3BP1; ras GTPase-activating protein-binding protein 1 isoform X1 [KO:K17265] [EC:5.6.2.3 3.6.4.13]
103664964  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
103665330  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
103666055  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103666985  [KO:K05414]
103667020  DDX58; antiviral innate immune response receptor RIG-I isoform X1 [KO:K12646] [EC:3.6.4.13]
103667294  CCL5; C-C motif chemokine 5 [KO:K12499]
103667295  [KO:K12964]
103667854  POLR3A; DNA-directed RNA polymerase III subunit RPC1 [KO:K03018] [EC:2.7.7.6]
103668439  POLR3K; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
103668524  MEFV; pyrin isoform X1 [KO:K12803]
103668714  ADAR; double-stranded RNA-specific adenosine deaminase isoform X1 [KO:K12968] [EC:3.5.4.37]
103668875  POLR3E; DNA-directed RNA polymerase III subunit RPC5 isoform X1 [KO:K14721]
103669780  SAMHD1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 isoform X1 [KO:K22544] [EC:3.1.5.-]
103670946  ZBP1; Z-DNA-binding protein 1 isoform X1 [KO:K12965]
103671004  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
103671072  FADD; FAS-associated death domain protein [KO:K02373]
103671092  IRF7; LOW QUALITY PROTEIN: interferon regulatory factor 7 [KO:K09447]
103671102  POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
103671366  PCBP1; poly(rC)-binding protein 1 [KO:K12889]
103671495  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
103672063  [KO:K20914]
103672157  POLR3G; DNA-directed RNA polymerase III subunit RPC7 isoform X2 [KO:K03024]
103673321  POLR3D; DNA-directed RNA polymerase III subunit RPC4 isoform X1 [KO:K03026]
103673727  ZDHHC1; palmitoyltransferase ZDHHC1 isoform X1 [KO:K20027] [EC:2.3.1.225]
103674082  POLR3H; DNA-directed RNA polymerase III subunit RPC8 isoform X1 [KO:K03022]
103674396  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
103674487  ZCCHC3; zinc finger CCHC domain-containing protein 3 [KO:K27162]
103674850  TREX1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
103676079  POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
103676392  POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
103676466  POLR3B; DNA-directed RNA polymerase III subunit RPC2 [KO:K03021] [EC:2.7.7.6]
103677059  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103678402  POLR3C; DNA-directed RNA polymerase III subunit RPC3 isoform X1 [KO:K03023]
103678410  POLR3GL; DNA-directed RNA polymerase III subunit RPC7-like [KO:K03024]
103679241  [KO:K20027] [EC:2.3.1.225]
103679293  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
103679584  RELA; transcription factor p65 [KO:K04735]
103679680  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103680385  [KO:K05414]
103680386  [KO:K05414]
103680527  POLR3F; DNA-directed RNA polymerase III subunit RPC6 isoform X1 [KO:K03025]
103680991  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
103681776  POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 isoform X1 [KO:K03013]
103682150  DNASE2; deoxyribonuclease-2-alpha [KO:K01158] [EC:3.1.22.1]
103682420  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
121103043  [KO:K05414]
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
umr04064  NF-kappa B signaling pathway
umr04120  Ubiquitin mediated proteolysis
umr04210  Apoptosis
umr04217  Necroptosis
umr04621  NOD-like receptor signaling pathway
umr04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   

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