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KEGG   PATHWAY: hsa04623
Entry
hsa04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Homo sapiens (human)
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
hsa04623  Cytosolic DNA-sensing pathway
hsa04623

Network
  Element
N00395  cGAS-STING signaling pathway
N01571  DNA degradation by extracellular/endolysosomal DNAse
Drug
D08978  Pralnacasan (USAN/INN)
D10416  Belnacasan (USAN/INN)
D11449  Etokimab (USAN)
D12352  Eclitasertib (USAN/INN)
D12375  Tozorakimab (USAN/INN)
D12720  Nibrozetone (USAN)
D12821  Flizasertib (USAN/INN)
D12846  Ocadusertib (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
11128  POLR3A; RNA polymerase III subunit A [KO:K03018] [EC:2.7.7.6]
55703  POLR3B; RNA polymerase III subunit B [KO:K03021] [EC:2.7.7.6]
10623  POLR3C; RNA polymerase III subunit C [KO:K03023]
661  POLR3D; RNA polymerase III subunit D [KO:K03026]
55718  POLR3E; RNA polymerase III subunit E [KO:K14721]
9533  POLR1C; RNA polymerase I and III subunit C [KO:K03027]
51728  POLR3K; RNA polymerase III subunit K [KO:K03019]
51082  POLR1D; RNA polymerase I and III subunit D [KO:K03020]
171568  POLR3H; RNA polymerase III subunit H [KO:K03022]
84265  POLR3GL; RNA polymerase III subunit GL [KO:K03024]
10622  POLR3G; RNA polymerase III subunit G [KO:K03024]
10621  POLR3F; RNA polymerase III subunit F [KO:K03025]
5434  POLR2E; RNA polymerase II, I and III subunit E [KO:K03013]
5435  POLR2F; RNA polymerase II, I and III subunit F [KO:K03014]
5437  POLR2H; RNA polymerase II, I and III subunit H [KO:K03016]
5440  POLR2K; RNA polymerase II, I and III subunit K [KO:K03009]
5441  POLR2L; RNA polymerase II, I and III subunit L [KO:K03007]
23586  RIGI; RNA sensor RIG-I [KO:K12646] [EC:5.6.2.6]
57506  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
3569  IL6; interleukin 6 [KO:K05405]
5093  PCBP1; poly(rC) binding protein 1 [KO:K12889]
10146  G3BP1; G3BP stress granule assembly factor 1 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
85364  ZCCHC3; zinc finger CCHC-type containing 3 [KO:K27162]
115004  CGAS; cyclic GMP-AMP synthase [KO:K17834] [EC:2.7.7.86]
340061  STING1; stimulator of interferon response cGAMP interactor 1 [KO:K12654]
29800  ZDHHC1; zinc finger DHHC-type containing 1 [KO:K20027] [EC:2.3.1.225]
653082  ZDHHC11B; zinc finger DHHC-type containing 11B [KO:K20027] [EC:2.3.1.225]
79844  ZDHHC11; zinc finger DHHC-type containing 11 [KO:K20027] [EC:2.3.1.225]
51428  DDX41; DEAD-box helicase 41 [KO:K13116] [EC:5.6.2.7]
3428  IFI16; interferon gamma inducible protein 16 [KO:K20914]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
9641  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
3661  IRF3; interferon regulatory factor 3 [KO:K05411]
3665  IRF7; interferon regulatory factor 7 [KO:K09447]
3439  IFNA1; interferon alpha 1 [KO:K05414]
3440  IFNA2; interferon alpha 2 [KO:K05414]
3441  IFNA4; interferon alpha 4 [KO:K05414]
3442  IFNA5; interferon alpha 5 [KO:K05414]
3443  IFNA6; interferon alpha 6 [KO:K05414]
3444  IFNA7; interferon alpha 7 [KO:K05414]
3445  IFNA8; interferon alpha 8 [KO:K05414]
3446  IFNA10; interferon alpha 10 [KO:K05414]
3447  IFNA13; interferon alpha 13 [KO:K05414]
3448  IFNA14; interferon alpha 14 [KO:K05414]
3449  IFNA16; interferon alpha 16 [KO:K05414]
3451  IFNA17; interferon alpha 17 [KO:K05414]
3452  IFNA21; interferon alpha 21 [KO:K05414]
3456  IFNB1; interferon beta 1 [KO:K05415]
81030  ZBP1; Z-DNA binding protein 1 [KO:K12965]
8737  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
11035  RIPK3; receptor interacting serine/threonine kinase 3 [KO:K08847] [EC:2.7.11.1]
8517  IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
4793  NFKBIB; NFKB inhibitor beta [KO:K02581]
4792  NFKBIA; NFKB inhibitor alpha [KO:K04734]
6351  CCL4; C-C motif chemokine ligand 4 [KO:K12964]
9560  CCL4L2; C-C motif chemokine ligand 4 like 2 [KO:K12964]
388372  CCL4L1; C-C motif chemokine ligand 4 like 1 [KO:K12964]
6352  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
3627  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
9447  AIM2; absent in melanoma 2 [KO:K12966]
114548  NLRP3; NLR family pyrin domain containing 3 [KO:K12800]
4210  MEFV; MEFV innate immunity regulator, pyrin [KO:K12803]
8772  FADD; Fas associated via death domain [KO:K02373]
841  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
29108  PYCARD; PYD and CARD domain containing [KO:K12799]
834  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
197259  MLKL; mixed lineage kinase domain like pseudokinase [KO:K08849] [EC:2.7.11.1]
836  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
840  CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
1687  GSDME; gasdermin E [KO:K22146]
79792  GSDMD; gasdermin D [KO:K20917]
3553  IL1B; interleukin 1 beta [KO:K04519]
3606  IL18; interleukin 18 [KO:K05482]
90865  IL33; interleukin 33 [KO:K12967]
103  ADAR; adenosine deaminase RNA specific [KO:K12968] [EC:3.5.4.37]
25939  SAMHD1; SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 [KO:K22544] [EC:3.1.5.-]
11277  TREX1; three prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
1777  DNASE2; deoxyribonuclease 2, lysosomal [KO:K01158] [EC:3.1.22.1]
58511  DNASE2B; deoxyribonuclease 2 beta [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
hsa04064  NF-kappa B signaling pathway
hsa04120  Ubiquitin mediated proteolysis
hsa04210  Apoptosis
hsa04217  Necroptosis
hsa04621  NOD-like receptor signaling pathway
hsa04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   

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Network (2)   
   KEGG NETWORK (2)   
Genome (1)   
   KEGG GENOME (1)   
Gene (83)   
   KEGG GENES (83)   
All databases (86)   

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