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KEGG   PATHWAY: hsa04623
hsa04623                    Pathway                                
Cytosolic DNA-sensing pathway - Homo sapiens (human)
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.
Organismal Systems; Immune system
Pathway map
hsa04623  Cytosolic DNA-sensing pathway

nt06161  Human immunodeficiency virus 1 (HIV-1)
nt06167  Human cytomegalovirus (HCMV)
nt06168  Herpes simplex virus 1 (HSV-1)
nt06182  Shigella
nt06520  CGAS-STING signaling
N00395  cGAS-STING signaling pathway
N01571  DNA degradation by extracellular/endolysosomal DNAse
D08978  Pralnacasan (USAN/INN)
D10416  Belnacasan (USAN/INN)
D11449  Etokimab (USAN)
D12352  Eclitasertib (USAN/INN)
D12375  Tozorakimab (USAN/INN)
D12720  Nibrozetone (USAN)
Homo sapiens (human) [GN:hsa]
11128  POLR3A; RNA polymerase III subunit A [KO:K03018] [EC:]
55703  POLR3B; RNA polymerase III subunit B [KO:K03021] [EC:]
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:]
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]
115004  CGAS; cyclic GMP-AMP synthase [KO:K17834] [EC:]
340061  STING1; stimulator of interferon response cGAMP interactor 1 [KO:K12654]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:]
9641  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:]
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:]
11035  RIPK3; receptor interacting serine/threonine kinase 3 [KO:K08847] [EC:]
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:]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:]
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:]
29108  PYCARD; PYD and CARD domain containing [KO:K12799]
834  CASP1; caspase 1 [KO:K01370] [EC:]
197259  MLKL; mixed lineage kinase domain like pseudokinase [KO:K08849] [EC:]
836  CASP3; caspase 3 [KO:K02187] [EC:]
840  CASP7; caspase 7 [KO:K04397] [EC:]
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:]
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:]
1777  DNASE2; deoxyribonuclease 2, lysosomal [KO:K01158] [EC:]
58511  DNASE2B; deoxyribonuclease 2 beta [KO:K01158] [EC:]
C00039  DNA
C20640  Cyclic GMP-AMP
Yanai H, Savitsky D, Tamura T, Taniguchi T
Regulation of the cytosolic DNA-sensing system in innate immunity: a current view.
Curr Opin Immunol 21:17-22 (2009)
Vilaysane A, Muruve DA
The innate immune response to DNA.
Semin Immunol 21:208-14 (2009)
Takeshita F, Ishii KJ
Intracellular DNA sensors in immunity.
Curr Opin Immunol 20:383-8 (2008)
Takaoka A, Shinohara S
DNA sensors in innate immune system.
Uirusu 58:37-46 (2008)
Takaoka A, Taniguchi T
Cytosolic DNA recognition for triggering innate immune responses.
Adv Drug Deliv Rev 60:847-57 (2008)
Kaiser WJ, Upton JW, Mocarski ES
Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors.
J Immunol 181:6427-34 (2008)
Rebsamen M, Heinz LX, Meylan E, Michallet MC, Schroder K, Hofmann K, Vazquez J, Benedict CA, Tschopp J
DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.
EMBO Rep 10:916-22 (2009)
Wang Z, Choi MK, Ban T, Yanai H, Negishi H, Lu Y, Tamura T, Takaoka A, Nishikura K, Taniguchi T
Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules.
Proc Natl Acad Sci U S A 105:5477-82 (2008)
Stetson DB, Ko JS, Heidmann T, Medzhitov R
Trex1 prevents cell-intrinsic initiation of autoimmunity.
Cell 134:587-98 (2008)
Schroder K, Muruve DA, Tschopp J
Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome.
Curr Biol 19:R262-5 (2009)
Krieg AM
AIMing 2 detect foreign DNA.
Sci Signal 2:pe39 (2009)
O'Neill LA
DNA makes RNA makes innate immunity.
Cell 138:428-30 (2009)
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
A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA.
Nat Immunol 7:40-8 (2006)
Cao X
New DNA-sensing pathway feeds RIG-I with RNA.
Nat Immunol 10:1049-51 (2009)
Sun L, Wu J, Du F, Chen X, Chen ZJ
Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.
Science 339:786-91 (2013)
Gao M, He Y, Tang H, Chen X, Liu S, Tao Y
cGAS/STING: novel perspectives of the classic pathway.
Mol Biomed 1:7 (2020)
Benjamin P, Sudhakar S, D'Arco F, Lobel U, Carney O, Roux CJ, Boddaert N, Hemingway C, Eleftheriou D, Mankad K
Spectrum of Neuroradiologic Findings Associated with Monogenic Interferonopathies.
AJNR Am J Neuroradiol 43:2-10 (2022)
Place DE, Lee S, Kanneganti TD
PANoptosis in microbial infection.
Curr Opin Microbiol 59:42-49 (2021)
Jiang W, Deng Z, Dai X, Zhao W
PANoptosis: A New Insight Into Oral Infectious Diseases.
Front Immunol 12:789610 (2021)
Wang Y, Kanneganti TD
From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways.
Comput Struct Biotechnol J 19:4641-4657 (2021)
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

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