KEGG   PATHWAY: ppad04623
Entry
ppad04623                   Pathway                                
Name
Cytosolic DNA-sensing pathway - Panthera pardus (leopard)
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
ppad04623  Cytosolic DNA-sensing pathway
ppad04623

Organism
Panthera pardus (leopard) [GN:ppad]
Gene
109264461  POLR3A; DNA-directed RNA polymerase III subunit RPC1 isoform X1 [KO:K03018] [EC:2.7.7.6]
109265458  POLR3B; DNA-directed RNA polymerase III subunit RPC2 isoform X1 [KO:K03021] [EC:2.7.7.6]
109259150  POLR3C; DNA-directed RNA polymerase III subunit RPC3 isoform X1 [KO:K03023]
109277353  POLR3D; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
109255523  POLR3E; DNA-directed RNA polymerase III subunit RPC5 [KO:K14721]
109271665  POLR1C; DNA-directed RNA polymerases I and III subunit RPAC1 isoform X1 [KO:K03027]
109261184  POLR3K; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
109266130  POLR1D; DNA-directed RNA polymerases I and III subunit RPAC2 [KO:K03020]
109265632  POLR3H; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
109259158  POLR3GL; DNA-directed RNA polymerase III subunit RPC7-like isoform X1 [KO:K03024]
109274872  POLR3G; DNA-directed RNA polymerase III subunit RPC7 isoform X1 [KO:K03024]
109274675  POLR3F; DNA-directed RNA polymerase III subunit RPC6 isoform X1 [KO:K03025]
109257738  POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 [KO:K03013]
109265557  POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
109275232  POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
109278018  POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
109252056  DDX58; probable ATP-dependent RNA helicase DDX58 isoform X1 [KO:K12646] [EC:5.6.2.6]
109274754  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
109247385  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109246747  RELA; transcription factor p65 isoform X1 [KO:K04735]
109263814  IL6; interleukin-6 isoform X1 [KO:K05405]
109262387  PCBP1; poly(rC)-binding protein 1 [KO:K12889]
109275989  G3BP1; ras GTPase-activating protein-binding protein 1 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
109272605  ZCCHC3; zinc finger CCHC domain-containing protein 3 [KO:K27162]
109248226  MB21D1; cyclic GMP-AMP synthase isoform X1 [KO:K17834] [EC:2.7.7.86]
109252151  TMEM173; stimulator of interferon genes protein [KO:K12654]
109260216  uncharacterized protein LOC109260216 isoform X1 [KO:K20027] [EC:2.3.1.225]
109270767  ZDHHC1; probable palmitoyltransferase ZDHHC1 isoform X1 [KO:K20027] [EC:2.3.1.225]
109261133  probable palmitoyltransferase ZDHHC11 [KO:K20027] [EC:2.3.1.225]
109267588  DDX41; probable ATP-dependent RNA helicase DDX41 isoform X1 [KO:K13116] [EC:5.6.2.7]
109257229  IFI16; gamma-interferon-inducible protein 16 isoform X1 [KO:K20914]
109270431  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
109257640  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
109253050  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
109259807  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
109247112  interferon alpha-2-like [KO:K05414]
109247120  interferon alpha-like [KO:K05414]
109247123  interferon alpha-like [KO:K05414]
109261306  interferon alpha-like [KO:K05414]
109261307  interferon alpha [KO:K05414]
109247124  IFNB1; interferon beta [KO:K05415]
109253479  ZBP1; Z-DNA-binding protein 1 isoform X1 [KO:K12965]
109249466  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
109254967  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
109261148  IKBKG; NF-kappa-B essential modulator [KO:K07210]
109261721  NF-kappa-B essential modulator-like [KO:K07210]
109272766  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
109262264  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
109269589  LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta-like [KO:K02581]
109256623  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
109253320  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109251966  C-C motif chemokine 4 [KO:K12964]
109251958  CCL5; C-C motif chemokine 5 [KO:K12499]
109277489  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
109260338  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
109278214  MEFV; pyrin isoform X1 [KO:K12803]
109246999  FADD; FAS-associated death domain protein [KO:K02373]
109260762  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
109259036  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
109251018  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
109272923  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
109263843  DFNA5; non-syndromic hearing impairment protein 5 [KO:K22146]
109258300  GSDMD; gasdermin-D [KO:K20917]
109264508  IL1B; interleukin-1 beta [KO:K04519]
109278654  IL18; interleukin-18 isoform X1 [KO:K05482]
109260126  IL33; interleukin-33 isoform X1 [KO:K12967]
109256299  ADAR; double-stranded RNA-specific adenosine deaminase isoform X1 [KO:K12968] [EC:3.5.4.37]
109272481  SAMHD1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 isoform X1 [KO:K22544] [EC:3.1.5.-]
109247764  TREX1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
109246178  DNASE2B; deoxyribonuclease-2-beta isoform X1 [KO:K01158] [EC:3.1.22.1]
109254029  DNASE2; LOW QUALITY PROTEIN: deoxyribonuclease-2-alpha [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
ppad04064  NF-kappa B signaling pathway
ppad04120  Ubiquitin mediated proteolysis
ppad04210  Apoptosis
ppad04217  Necroptosis
ppad04621  NOD-like receptor signaling pathway
ppad04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   
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