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
Cytosolic DNA-sensing pathway
hsa04623

All organismsOrtholog table
Module
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)
Drug
D08978  
Pralnacasan (USAN/INN)
D10416  
Belnacasan (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
11128  
POLR3A; polymerase (RNA) III subunit A [KO:K03018] [EC:2.7.7.6]
55703  
POLR3B; polymerase (RNA) III subunit B [KO:K03021] [EC:2.7.7.6]
10623  
POLR3C; polymerase (RNA) III subunit C [KO:K03023]
661  
POLR3D; polymerase (RNA) III subunit D [KO:K03026]
55718  
POLR3E; polymerase (RNA) III subunit E [KO:K14721]
DNA-directed RNA polymerase III subunit RPC5; K14721 DNA-directed RNA polymerase III subunit RPC5 [KO:K14721]
9533  
POLR1C; polymerase (RNA) I subunit C [KO:K03027]
51728  
POLR3K; polymerase (RNA) III subunit K [KO:K03019]
51082  
POLR1D; polymerase (RNA) I subunit D [KO:K03020]
171568  
POLR3H; polymerase (RNA) III subunit H [KO:K03022]
84265  
POLR3GL; polymerase (RNA) III subunit G like [KO:K03024]
10622  
POLR3G; polymerase (RNA) III subunit G [KO:K03024]
10621  
POLR3F; polymerase (RNA) III subunit F [KO:K03025]
5434  
POLR2E; polymerase (RNA) II subunit E [KO:K03013]
5435  
POLR2F; polymerase (RNA) II subunit F [KO:K03014]
5437  
POLR2H; polymerase (RNA) II subunit H [KO:K03016]
5440  
POLR2K; polymerase (RNA) II subunit K [KO:K03009]
5441  
POLR2L; polymerase (RNA) 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  
MB21D1; Mab-21 domain containing 1 [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 kappa light polypeptide gene enhancer in B-cells, kinase 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 kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase 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)
Reference
  Authors
Vilaysane A, Muruve DA
  Title
The innate immune response to DNA.
  Journal
Semin Immunol 21:208-14 (2009)
Reference
  Authors
Takeshita F, Ishii KJ
  Title
Intracellular DNA sensors in immunity.
  Journal
Curr Opin Immunol 20:383-8 (2008)
Reference
  Authors
Takaoka A, Shinohara S
  Title
DNA sensors in innate immune system.
  Journal
Uirusu 58:37-46 (2008)
Reference
  Authors
Takaoka A, Taniguchi T
  Title
Cytosolic DNA recognition for triggering innate immune responses.
  Journal
Adv Drug Deliv Rev 60:847-57 (2008)
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)
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)
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)
Reference
  Authors
Stetson DB, Ko JS, Heidmann T, Medzhitov R
  Title
Trex1 prevents cell-intrinsic initiation of autoimmunity.
  Journal
Cell 134:587-98 (2008)
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)
Reference
  Authors
Krieg AM
  Title
AIMing 2 detect foreign DNA.
  Journal
Sci Signal 2:pe39 (2009)
Reference
  Authors
O'Neill LA
  Title
DNA makes RNA makes innate immunity.
  Journal
Cell 138:428-30 (2009)
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)
Reference
  Authors
Cao X
  Title
New DNA-sensing pathway feeds RIG-I with RNA.
  Journal
Nat Immunol 10:1049-51 (2009)
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)
KO pathway
 

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