KEGG   PATHWAY: hsa04622Help
Entry
hsa04622                    Pathway                                

Name
RIG-I-like receptor signaling pathway - Homo sapiens (human)
Description
Specific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular viral replication is recognized by a family of cytosolic RNA helicases termed RIG-I-like receptors (RLRs). The RLR proteins include RIG-I, MDA5, and LGP2 and are expressed in both immune and nonimmune cells. Upon recognition of viral nucleic acids, RLRs recruit specific intracellular adaptor proteins to initiate signaling pathways that lead to the synthesis of type I interferon and other inflammatory cytokines, which are important for eliminating viruses.
Class
Organismal Systems; Immune system
BRITE hierarchy
Pathway map
hsa04622  RIG-I-like receptor signaling pathway
hsa04622

Ortholog table
Network
nt06133  RIG-I signaling (viruses)
nt06162  Hepatitis B virus (HBV)
nt06163  Hepatitis C virus (HCV)
nt06165  Epstein-Barr virus (EBV)
nt06168  Herpes simplex virus 1 (HSV-1)
nt06169  Measles virus (MV)
nt06170  Influenza A virus (IAV)
nt06263  Hepatocellular carcinoma
  Element
N00469  RIG-I-IRF7/3 signaling pathway
N00688  RIG-I-NFKB signaling pathway
Disease
H00290  Aicardi-Goutieres syndrome
H00827  Brooke-Spiegler syndrome
H00882  Cocoon syndrome
H01746  STING-associated vasculopathy with onset in infancy
Organism
Homo sapiens (human) [GN:hsa]
Gene
23586  DDX58; DExD/H-box helicase 58 [KO:K12646] [EC:3.6.4.13]
64135  IFIH1; interferon induced with helicase C domain 1 [KO:K12647] [EC:3.6.4.13]
57506  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
79132  DHX58; DExH-box helicase 58 [KO:K12649] [EC:3.6.4.13]
7187  TRAF3; TNF receptor associated factor 3 [KO:K03174]
10010  TANK; TRAF family member associated NFKB activator [KO:K12650]
64343  AZI2; 5-azacytidine induced 2 [KO:K12651]
9755  TBKBP1; TBK1 binding protein 1 [KO:K12652]
8517  IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]
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]
3467  IFNW1; interferon omega 1 [KO:K05440]
338376  IFNE; interferon epsilon [KO:K05442]
56832  IFNK; interferon kappa [KO:K05441]
8717  TRADD; TNFRSF1A associated via death domain [KO:K03171]
8772  FADD; Fas associated via death domain [KO:K02373]
8737  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
841  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
843  CASP10; caspase 10 [KO:K04400] [EC:3.4.22.63]
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]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
7186  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
7189  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
4214  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
3576  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
7124  TNF; tumor necrosis factor [KO:K03156]
3592  IL12A; interleukin 12A [KO:K05406]
3593  IL12B; interleukin 12B [KO:K05425]
3627  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
7706  TRIM25; tripartite motif containing 25 [KO:K10652] [EC:2.3.2.27]
1540  CYLD; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
54941  RNF125; ring finger protein 125 [KO:K12170] [EC:2.3.2.27]
9636  ISG15; ISG15 ubiquitin like modifier [KO:K12159]
9474  ATG5; autophagy related 5 [KO:K08339]
9140  ATG12; autophagy related 12 [KO:K08336]
79671  NLRX1; NLR family member X1 [KO:K12653]
340061  STING1; stimulator of interferon response cGAMP interactor 1 [KO:K12654]
55593  OTUD5; OTU deubiquitinase 5 [KO:K12655] [EC:3.4.19.12]
80143  SIKE1; suppressor of IKBKE 1 [KO:K12656]
1654  DDX3X; DEAD-box helicase 3 X-linked [KO:K11594] [EC:3.6.4.13]
5300  PIN1; peptidylprolyl cis/trans isomerase, NIMA-interacting 1 [KO:K09578] [EC:5.2.1.8]
26007  TKFC; triokinase and FMN cyclase [KO:K00863] [EC:2.7.1.28 2.7.1.29 4.6.1.15]
Reference
  Authors
Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T
  Title
The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
  Journal
Nat Immunol 5:730-7 (2004)
DOI:10.1038/ni1087
Reference
  Authors
Takeuchi O, Akira S
  Title
MDA5/RIG-I and virus recognition.
  Journal
Curr Opin Immunol 20:17-22 (2008)
DOI:10.1016/j.coi.2008.01.002
Reference
  Authors
Yoneyama M, Fujita T
  Title
RNA recognition and signal transduction by RIG-I-like receptors.
  Journal
Immunol Rev 227:54-65 (2009)
DOI:10.1111/j.1600-065X.2008.00727.x
Reference
  Authors
Nakhaei P, Genin P, Civas A, Hiscott J
  Title
RIG-I-like receptors: sensing and responding to RNA virus infection.
  Journal
Semin Immunol 21:215-22 (2009)
DOI:10.1016/j.smim.2009.05.001
Reference
  Authors
Moore CB, Ting JP
  Title
Regulation of mitochondrial antiviral signaling pathways.
  Journal
Immunity 28:735-9 (2008)
DOI:10.1016/j.immuni.2008.05.005
Reference
  Authors
Barral PM, Sarkar D, Su ZZ, Barber GN, DeSalle R, Racaniello VR, Fisher PB
  Title
Functions of the cytoplasmic RNA sensors RIG-I and MDA-5: key regulators of innate immunity.
  Journal
Pharmacol Ther 124:219-34 (2009)
DOI:10.1016/j.pharmthera.2009.06.012
Reference
  Authors
Schlee M, Hartmann E, Coch C, Wimmenauer V, Janke M, Barchet W, Hartmann G
  Title
Approaching the RNA ligand for RIG-I?
  Journal
Immunol Rev 227:66-74 (2009)
DOI:10.1111/j.1600-065X.2008.00724.x
Reference
  Authors
Saito T, Gale M Jr
  Title
Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity.
  Journal
J Exp Med 205:1523-7 (2008)
DOI:10.1084/jem.20081210
Reference
  Authors
Kawai T, Akira S
  Title
Toll-like receptor and RIG-I-like receptor signaling.
  Journal
Ann N Y Acad Sci 1143:1-20 (2008)
DOI:10.1196/annals.1443.020
Reference
  Authors
Michallet MC, Meylan E, Ermolaeva MA, Vazquez J, Rebsamen M, Curran J, Poeck H, Bscheider M, Hartmann G, Konig M, Kalinke U, Pasparakis M, Tschopp J
  Title
TRADD protein is an essential component of the RIG-like helicase antiviral pathway.
  Journal
Immunity 28:651-61 (2008)
DOI:10.1016/j.immuni.2008.03.013
Reference
  Authors
Yoshida R, Takaesu G, Yoshida H, Okamoto F, Yoshioka T, Choi Y, Akira S, Kawai T, Yoshimura A, Kobayashi T
  Title
TRAF6 and MEKK1 play a pivotal role in the RIG-I-like helicase antiviral pathway.
  Journal
J Biol Chem 283:36211-20 (2008)
DOI:10.1074/jbc.M806576200
Reference
  Authors
Mikkelsen SS, Jensen SB, Chiliveru S, Melchjorsen J, Julkunen I, Gaestel M, Arthur JS, Flavell RA, Ghosh S, Paludan SR
  Title
RIG-I-mediated activation of p38 MAPK is essential for viral induction of interferon and activation of dendritic cells: dependence on TRAF2 and TAK1.
  Journal
J Biol Chem 284:10774-82 (2009)
DOI:10.1074/jbc.M807272200
Related
pathway
hsa04010  MAPK signaling pathway
hsa04120  Ubiquitin mediated proteolysis
hsa04210  Apoptosis
hsa04630  JAK-STAT signaling pathway
KO pathway
ko04622   
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