KEGG   PATHWAY: oas04623
Entry
oas04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Ovis aries (sheep)
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
oas04623  Cytosolic DNA-sensing pathway
oas04623

Organism
Ovis aries (sheep) [GN:oas]
Gene
101104715  POLR3A; DNA-directed RNA polymerase III subunit RPC1 isoform X2 [KO:K03018] [EC:2.7.7.6]
101115446  POLR3B; DNA-directed RNA polymerase III subunit RPC2 isoform X1 [KO:K03021] [EC:2.7.7.6]
101116616  POLR3C; DNA-directed RNA polymerase III subunit RPC3 isoform X1 [KO:K03023]
101116536  POLR3D; DNA-directed RNA polymerase III subunit RPC4 isoform X2 [KO:K03026]
101103692  POLR3E; DNA-directed RNA polymerase III subunit RPC5 isoform X1 [KO:K14721]
101114821  POLR1C; DNA-directed RNA polymerases I and III subunit RPAC1 [KO:K03027]
101107752  POLR3K; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
101114283  POLR1D; DNA-directed RNA polymerases I and III subunit RPAC2 [KO:K03020]
101111182  POLR3H; DNA-directed RNA polymerase III subunit RPC8 isoform X1 [KO:K03022]
101118651  POLR3GL; DNA-directed RNA polymerase III subunit RPC7-like isoform X4 [KO:K03024]
101106586  POLR3G; DNA-directed RNA polymerase III subunit RPC7 isoform X8 [KO:K03024]
101121955  POLR3F; DNA-directed RNA polymerase III subunit RPC6 isoform X2 [KO:K03025]
105607815  DNA-directed RNA polymerase III subunit RPC6-like [KO:K03025]
101116826  POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 isoform X2 [KO:K03013]
101103555  POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
101119867  POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
101104250  POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
114117498  DNA-directed RNA polymerases I, II, and III subunit RPABC4-like [KO:K03009]
105604154  POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
101107257  RIGI; antiviral innate immune response receptor RIG-I [KO:K12646] [EC:5.6.2.6]
101119838  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
101108228  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
101102191  RELA; transcription factor p65 [KO:K04735]
443406  IL6; interleukin-6 precursor [KO:K05405]
101106505  PCBP1; poly(rC)-binding protein 1 [KO:K12889]
101106523  G3BP1; ras GTPase-activating protein-binding protein 1 isoform X2 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
105611500  ras GTPase-activating protein-binding protein 1 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
132658622  ras GTPase-activating protein-binding protein 1-like [KO:K17265] [EC:5.6.2.5 5.6.2.3]
101108507  ZCCHC3; zinc finger CCHC domain-containing protein 3 [KO:K27162]
114116050  CGAS; cyclic GMP-AMP synthase [KO:K17834] [EC:2.7.7.86]
101116050  STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]
101108247  ZDHHC1; palmitoyltransferase ZDHHC1 isoform X2 [KO:K20027] [EC:2.3.1.225]
101109601  palmitoyltransferase ZDHHC11-like isoform X1 [KO:K20027] [EC:2.3.1.225]
101102307  DDX41; probable ATP-dependent RNA helicase DDX41 [KO:K13116] [EC:5.6.2.7]
101112936  interferon-activable protein 203 isoform X2 [KO:K20914]
101110830  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
101116923  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
780485  IRF3; interferon regulatory factor 3 [KO:K05411]
101103683  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
101111435  interferon alpha-H-like [KO:K05414]
105601948  interferon alpha-H-like [KO:K05414]
492823  IFN1; interferon alpha-1 [KO:K05414]
101102963  interferon alpha-H-like [KO:K05414]
101105135  interferon alpha-H [KO:K05414]
101103872  interferon alpha-2-like [KO:K05414]
114113084  interferon alpha-14-like [KO:K05414]
114113089  interferon alpha-2-like [KO:K05414]
114113090  interferon alpha-H-like [KO:K05414]
114112827  interferon alpha-3-like [KO:K05414]
101105632  interferon alpha-H-like [KO:K05414]
121818512  interferon alpha-2-like [KO:K05414]
101103702  interferon beta-2-like [KO:K05415]
101103376  interferon beta-2-like [KO:K05415]
101103623  interferon beta-2 [KO:K05415]
114113004  interferon beta-2-like [KO:K05415]
114113016  interferon beta-2-like [KO:K05415]
114113206  interferon beta-2-like [KO:K05415]
114112819  interferon beta-2-like [KO:K05415]
114112835  interferon beta-2-like [KO:K05415]
114112840  interferon beta-2-like [KO:K05415]
114112883  interferon beta-2 [KO:K05415]
114112830  interferon beta-2-like [KO:K05415]
121818657  interferon beta-2-like [KO:K05415]
101104169  ZBP1; Z-DNA-binding protein 1 isoform X3 [KO:K12965]
101110186  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
101118877  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
101107332  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
101111143  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
780484  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
101113618  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
780520  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101114285  C-C motif chemokine 4 [KO:K12964]
101115553  CCL5; C-C motif chemokine 5 [KO:K12499]
442997  CXCL10; C-X-C motif chemokine 10 precursor [KO:K12671]
121818640  AIM2; LOW QUALITY PROTEIN: interferon-inducible protein AIM2 [KO:K12966]
101107699  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
101121821  MEFV; pyrin isoform X1 [KO:K12803]
101116783  FADD; FAS-associated death domain protein [KO:K02373]
101107334  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101105208  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101117013  CASP1; caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
101115147  MLKL; mixed lineage kinase domain-like protein isoform X4 [KO:K08849] [EC:2.7.11.1]
443031  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
101122741  CASP7; caspase-7 isoform X2 [KO:K04397] [EC:3.4.22.60]
101109266  GSDME; gasdermin-E [KO:K22146]
101117254  GSDMD; gasdermin-D isoform X1 [KO:K20917]
443539  IL1B; interleukin-1 beta precursor [KO:K04519]
443206  IL18; interleukin-18 [KO:K05482]
101116705  IL33; interleukin-33 isoform X1 [KO:K12967]
101123484  SAMHD1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 isoform X4 [KO:K22544] [EC:3.1.5.-]
101119766  TREX1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
101110100  DNASE2B; deoxyribonuclease-2-beta [KO:K01158] [EC:3.1.22.1]
101105493  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
oas04064  NF-kappa B signaling pathway
oas04120  Ubiquitin mediated proteolysis
oas04210  Apoptosis
oas04217  Necroptosis
oas04621  NOD-like receptor signaling pathway
oas04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   
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