KEGG PATHWAY: hsa04623

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

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)

Drug

D08978

Pralnacasan (USAN/INN)

Organism

Homo sapiens (human) [GN:hsa]

Gene

11128	POLR3A; polymerase (RNA) III (DNA directed) polypeptide A, 155kDa [KO:K03018] [EC:2.7.7.6]
55703	POLR3B; polymerase (RNA) III (DNA directed) polypeptide B [KO:K03021] [EC:2.7.7.6]
10623	POLR3C; polymerase (RNA) III (DNA directed) polypeptide C (62kD) [KO:K03023]
101060460	DNA-directed RNA polymerase III subunit RPC3-like; K03023 DNA-directed RNA polymerase III subunit RPC3 [KO:K03023]
661	POLR3D; polymerase (RNA) III (DNA directed) polypeptide D, 44kDa [KO:K03026]
55718	POLR3E; polymerase (RNA) III (DNA directed) polypeptide E (80kD) [KO:K14721]
101060521	DNA-directed RNA polymerase III subunit RPC5-like; K14721 DNA-directed RNA polymerase III subunit RPC5 [KO:K14721]
9533	POLR1C; polymerase (RNA) I polypeptide C, 30kDa [KO:K03027]
51728	POLR3K; polymerase (RNA) III (DNA directed) polypeptide K, 12.3 kDa [KO:K03019]
51082	POLR1D; polymerase (RNA) I polypeptide D, 16kDa [KO:K03020]
171568	POLR3H; polymerase (RNA) III (DNA directed) polypeptide H (22.9kD) [KO:K03022]
84265	POLR3GL; polymerase (RNA) III (DNA directed) polypeptide G (32kD)-like [KO:K03024]
10622	POLR3G; polymerase (RNA) III (DNA directed) polypeptide G (32kD) [KO:K03024]
101060555	DNA-directed RNA polymerase III subunit RPC7-like; K03024 DNA-directed RNA polymerase III subunit RPC7 [KO:K03024]
10621	POLR3F; polymerase (RNA) III (DNA directed) polypeptide F, 39 kDa [KO:K03025]
5434	POLR2E; polymerase (RNA) II (DNA directed) polypeptide E, 25kDa [KO:K03013]
5435	POLR2F; polymerase (RNA) II (DNA directed) polypeptide F [KO:K03014]
5437	POLR2H; polymerase (RNA) II (DNA directed) polypeptide H [KO:K03016]
5440	POLR2K; polymerase (RNA) II (DNA directed) polypeptide K, 7.0kDa [KO:K03009]
5441	POLR2L; polymerase (RNA) II (DNA directed) polypeptide L, 7.6kDa [KO:K03007]
23586	DDX58; DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 [KO:K12646] [EC:3.6.3.14]
57506	MAVS; mitochondrial antiviral signaling protein [KO:K12648]
4790	NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970	RELA; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
3569	IL6; interleukin 6 (interferon, beta 2) [KO:K05405]
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, fibroblast [KO:K05415]
81030	ZBP1; Z-DNA binding protein 1 [KO:K12965]
8737	RIPK1; receptor (TNFRSF)-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; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta [KO:K02581]
4792	NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
6351	CCL4; chemokine (C-C motif) ligand 4 [KO:K12964]
9560	CCL4L1; chemokine (C-C motif) ligand 4-like 1 [KO:K12964]
388372	CCL4L2; chemokine (C-C motif) ligand 4-like 2 [KO:K12964]
101060278	c-C motif chemokine 4-like; K12964 C-C motif chemokine 4 [KO:K12964]
6352	CCL5; chemokine (C-C motif) ligand 5 [KO:K12499]
3627	CXCL10; chemokine (C-X-C motif) 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, apoptosis-related cysteine peptidase [KO:K01370] [EC:3.4.22.36]
3553	IL1B; interleukin 1, beta [KO:K04519]
3606	IL18; interleukin 18 (interferon-gamma-inducing factor) [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.-]

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)

Reference

PMID:19497760

Authors

Vilaysane A, Muruve DA

Title

The innate immune response to DNA.

Journal

Semin Immunol 21:208-14 (2009)

Reference

PMID:18573338

Authors

Takeshita F, Ishii KJ

Title

Intracellular DNA sensors in immunity.

Journal

Curr Opin Immunol 20:383-8 (2008)

Reference

PMID:19122387

Authors

Takaoka A, Shinohara S

Title

DNA sensors in innate immune system.

Journal

Uirusu 58:37-46 (2008)

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)

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)

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)

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)

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)

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)

Reference

PMID:19567913

Authors

Krieg AM

Title

AIMing 2 detect foreign DNA.

Journal

Sci Signal 2:pe39 (2009)

Reference

PMID:19665965

Authors

O'Neill LA

Title

DNA makes RNA makes innate immunity.

Journal

Cell 138:428-30 (2009)

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)

Reference

PMID:19767723

Authors

Cao X

Title

New DNA-sensing pathway feeds RIG-I with RNA.

Journal

Nat Immunol 10:1049-51 (2009)

KO pathway

ko04623

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Ontology (1)   
   KEGG BRITE (1)   
Pathway (2)   
   KEGG MODULE (1)   
   BioSystems (1)   
Disease (5)   
   KEGG DISEASE (5)   
Drug (1)   
   KEGG DRUG (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (66)   
   KEGG GENES (66)   
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