KEGG   PATHWAY: hsa04623Help
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
BRITE hierarchy
Pathway map
hsa04623  Cytosolic DNA-sensing pathway
hsa04623

Ortholog table
Module
hsa_M00181  RNA polymerase III, eukaryotes [PATH:hsa04623]
Disease
H00290  Aicardi-Goutieres syndrome (AGS)
H00291  Familial chilblain lupus (FCL)
H00880  Dyschromatosis symmetrica hereditaria
H00882  Cocoon syndrome
H01000  Retinal vasculopathy with cerebral leukodystrophy (RVCL)
H01746  STING-associated vasculopathy with onset in infancy (SAVI)
Drug
D08978  Pralnacasan (USAN/INN)
D10416  Belnacasan (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 G like [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 subunit E [KO:K03013]
5435  POLR2F; RNA polymerase II subunit F [KO:K03014]
5437  POLR2H; RNA polymerase II subunit H [KO:K03016]
5440  POLR2K; RNA polymerase II subunit K [KO:K03009]
5441  POLR2L; RNA polymerase II subunit L [KO:K03007]
23586  DDX58; DExD/H-box helicase 58 [KO:K12646] [EC:3.6.3.14]
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:2.7.7.86]
340061  TMEM173; transmembrane protein 173 [KO:K12654]
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 subunit gamma [KO:K07210]
1147  CHUK; conserved helix-loop-helix ubiquitous kinase [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]
29108  PYCARD; PYD and CARD domain containing [KO:K12799]
834  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
3553  IL1B; interleukin 1 beta [KO:K04519]
3606  IL18; interleukin 18 [KO:K05482]
90865  IL33; interleukin 33 [KO:K12967]
11277  TREX1; three prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
103  ADAR; adenosine deaminase, RNA specific [KO:K12968] [EC:3.5.4.37]
Compound
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
KO pathway
ko04623   

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