KEGG PATHWAY: rtp04621

KEGG

PATHWAY: rtp04621

Entry

rtp04621                    Pathway

Name

NOD-like receptor signaling pathway - Rhincodon typus (whale shark)

Description

Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains more than 20 members in mammals and plays a pivotal role in the recognition of intracellular ligands. NOD1 and NOD2, two prototypic NLRs, sense the cytosolic presence of the bacterial peptidoglycan fragments that escaped from endosomal compartments, driving the activation of NF-{kappa}B and MAPK, cytokine production and apoptosis. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. The activated of caspase-1 regulates maturation of the pro-inflammatory cytokines IL-1B, IL-18 and drives pyroptosis.

Class

Organismal Systems; Immune system

Pathway map

NOD-like receptor signaling pathway

Organism

Rhincodon typus (whale shark) [GN:rtp]

Gene

nucleotide-binding oligomerization domain-containing protein 1-like [KO:K08727]

nucleotide-binding oligomerization domain-containing protein 1-like isoform X1 [KO:K08727]

nucleotide-binding oligomerization domain-containing protein 1-like isoform X1 [KO:K08727]

receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]

chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]

ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]

NF-kappa-B inhibitor alpha-like [KO:K04734]

nfkbiab; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha b [KO:K04734]

nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]

uncharacterized protein LOC109919113 [KO:K05482]

interleukin-6-like [KO:K05405]

il6; interleukin-6 [KO:K05405]

interleukin-6-like [KO:K05405]

tumor necrosis factor-like [KO:K03156]

tumor necrosis factor-like [KO:K03156]

lymphotoxin-alpha-like [KO:K03156]

tumor necrosis factor-like [KO:K03156]

tumor necrosis factor-like [KO:K03156]

interleukin-8-like [KO:K10030]

interleukin-8-like [KO:K10030]

interleukin-8-like [KO:K10030]

interleukin-8-like [KO:K10030]

interleukin-8-like [KO:K10030]

interleukin-8-like [KO:K10030]

interleukin-8-like [KO:K10030]

interleukin-8-like [KO:K10030]

interleukin-8-like [KO:K10030]

nod2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]

map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]

tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]

tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]

mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]

mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]

mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]

mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]

mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]

mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]

mitogen-activated protein kinase 14B-like [KO:K04441] [EC:2.7.11.24]

mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]

jun; transcription factor AP-1 [KO:K04448]

autophagy-related protein 16-1-like isoform X1 [KO:K17890]

uncharacterized protein LOC109914975 isoform X1 [KO:K17890]

autophagy-related protein 16-1-like [KO:K17890]

atg5; autophagy protein 5 isoform X1 [KO:K08339]

gamma-aminobutyric acid receptor-associated protein [KO:K08341]

gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]

map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]

microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]

microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]

map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]

sugt1; protein SGT1 homolog [KO:K12795]

ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K20894]

ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]

si:dkey-181m9.8; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]

E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]

lipoma-preferred partner homolog isoform X2 [KO:K12792]

erbin; erbin isoform X1 [KO:K12796]

inhibitor of apoptosis protein-like [KO:K16060]

TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]

traf2b; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]

TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]

traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]

tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]

traf3; TNF receptor-associated factor 3 isoform X2 [KO:K03174]

serine/threonine-protein kinase TBK1-like [KO:K05410] [EC:2.7.11.10]

serine/threonine-protein kinase TBK1-like isoform X1 [KO:K05410] [EC:2.7.11.10]

TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]

interferon regulatory factor 8-like [KO:K09447]

interferon a3-like [KO:K05414]

interferon alpha-F-like [KO:K05414]

interferon alpha-10-like [KO:K05414]

interferon alpha-1/13-like [KO:K05414]

interferon beta-like [KO:K05414]

nlrx1; NLR family member X1 [KO:K12653]

caspase-1-like isoform X3 [KO:K01370] [EC:3.4.22.36]

apoptosis regulator Bcl-2-like isoform X2 [KO:K02161]

cathepsin B [KO:K01363] [EC:3.4.22.1]

LOW QUALITY PROTEIN: extracellular calcium-sensing receptor-like [KO:K04612]

G-protein coupled receptor family C group 6 member A-like [KO:K04622]

G-protein coupled receptor family C group 6 member A-like [KO:K04622]

gprc6a; G-protein coupled receptor family C group 6 member A [KO:K04622]

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like isoform X1 [KO:K05858] [EC:3.1.4.11]

itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]

voltage-dependent anion-selective channel protein 1 isoform X3 [KO:K05862]

voltage-dependent anion-selective channel protein 2 [KO:K15040]

vdac3; voltage-dependent anion-selective channel protein 3 [KO:K15041]

mcu; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]

2-5A-dependent ribonuclease [KO:K01165]

dhx33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]

mitofusin-2-like [KO:K21356] [EC:3.6.5.-]

mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]

ripk1l; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]

dnm1l; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]

nampt1; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]

cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]

cytochrome b-245 light chain [KO:K08009]

thioredoxin-interacting protein-like [KO:K20910]

txn2; thioredoxin, mitochondrial [KO:K03671]

thioredoxin-like [KO:K03671]

thioredoxin-like isoform X2 [KO:K03671]

thioredoxin-like [KO:K03671]

thioredoxin-like [KO:K03671]

brcc3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]

hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]

heat shock protein HSP 90-alpha [KO:K04079]

caspase-8-like [KO:K04398] [EC:3.4.22.61]

fadd; protein FADD [KO:K02373]

baculoviral IAP repeat-containing protein 1-like isoform X1 [KO:K12807]

NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]

protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]

transforming protein RhoA isoform X1 [KO:K04513]

serine/threonine-protein kinase N2-like [KO:K23691] [EC:2.7.11.13]

ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 [KO:K06630]

uncharacterized protein LOC109928467 isoform X1 [KO:K05131]

jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]

tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]

signal transducer and activator of transcription 1-alpha/beta [KO:K11220]

myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]

interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]

sting1; stimulator of interferon genes protein isoform X1 [KO:K12654]

Compound

ATP

Calcium cation

L-Homocysteine

Potassium cation

Nitric oxide

D-myo-Inositol 1,4,5-trisphosphate

Reference

Authors

Vandenabeele P, Bertrand MJ

Title

The role of the IAP E3 ubiquitin ligases in regulating pattern-recognition receptor signalling.

Journal

Nat Rev Immunol 12:833-44 (2012)
DOI:10.1038/nri3325

Reference

Authors

Strober W, Murray PJ, Kitani A, Watanabe T

Title

Signalling pathways and molecular interactions of NOD1 and NOD2.

Journal

Nat Rev Immunol 6:9-20 (2006)
DOI:10.1038/nri1747

Reference

Authors

Estornes Y, Bertrand MJ

Title

IAPs, regulators of innate immunity and inflammation.

Journal

Semin Cell Dev Biol 39:106-14 (2015)
DOI:10.1016/j.semcdb.2014.03.035

Reference

Authors

Jakopin Z

Title

Nucleotide-binding oligomerization domain (NOD) inhibitors: a rational approach toward inhibition of NOD signaling pathway.

Journal

J Med Chem 57:6897-918 (2014)
DOI:10.1021/jm401841p

Reference

Authors

Caruso R, Warner N, Inohara N, Nunez G

Title

NOD1 and NOD2: signaling, host defense, and inflammatory disease.

Journal

Immunity 41:898-908 (2014)
DOI:10.1016/j.immuni.2014.12.010

Reference

Authors

Murray PJ

Title

Beyond peptidoglycan for Nod2.

Journal

Nat Immunol 10:1053-4 (2009)
DOI:10.1038/ni1009-1053

Reference

Authors

Lecat A, Piette J, Legrand-Poels S

Title

The protein Nod2: an innate receptor more complex than previously assumed.

Journal

Biochem Pharmacol 80:2021-31 (2010)
DOI:10.1016/j.bcp.2010.07.016

Reference

Authors

Man SM, Kanneganti TD

Title

Converging roles of caspases in inflammasome activation, cell death and innate immunity.

Journal

Nat Rev Immunol 16:7-21 (2016)
DOI:10.1038/nri.2015.7

Reference

Authors

Broz P, Dixit VM

Title

Inflammasomes: mechanism of assembly, regulation and signalling.

Journal

Nat Rev Immunol 16:407-20 (2016)
DOI:10.1038/nri.2016.58

Reference

Authors

Man SM, Kanneganti TD

Title

Regulation of inflammasome activation.

Journal

Immunol Rev 265:6-21 (2015)
DOI:10.1111/imr.12296

Reference

Authors

Jo EK, Kim JK, Shin DM, Sasakawa C

Title

Molecular mechanisms regulating NLRP3 inflammasome activation.

Journal

Cell Mol Immunol 13:148-59 (2016)
DOI:10.1038/cmi.2015.95

Reference

Authors

Broz P, Monack DM

Title

Newly described pattern recognition receptors team up against intracellular pathogens.

Journal

Nat Rev Immunol 13:551-65 (2013)
DOI:10.1038/nri3479

Reference

Authors

Rathinam VA, Vanaja SK, Fitzgerald KA

Title

Regulation of inflammasome signaling.

Journal

Nat Immunol 13:333-42 (2012)
DOI:10.1038/ni.2237

Reference

Authors

Sutterwala FS, Haasken S, Cassel SL

Title

Mechanism of NLRP3 inflammasome activation.

Journal

Ann N Y Acad Sci 1319:82-95 (2014)
DOI:10.1111/nyas.12458

Reference

Authors

Latz E, Xiao TS, Stutz A

Title

Activation and regulation of the inflammasomes.

Journal

Nat Rev Immunol 13:397-411 (2013)
DOI:10.1038/nri3452

Reference

Authors

Blander JM

Title

A long-awaited merger of the pathways mediating host defence and programmed cell death.

Journal

Nat Rev Immunol 14:601-18 (2014)
DOI:10.1038/nri3720

Reference

Authors

von Moltke J, Ayres JS, Kofoed EM, Chavarria-Smith J, Vance RE

Title

Recognition of bacteria by inflammasomes.

Journal

Annu Rev Immunol 31:73-106 (2013)
DOI:10.1146/annurev-immunol-032712-095944

Reference

Authors

Abais JM, Xia M, Zhang Y, Boini KM, Li PL

Title

Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector?

Journal

Antioxid Redox Signal 22:1111-29 (2015)
DOI:10.1089/ars.2014.5994

Reference

Authors

Storek KM, Monack DM

Title

Bacterial recognition pathways that lead to inflammasome activation.

Journal

Immunol Rev 265:112-29 (2015)
DOI:10.1111/imr.12289

Reference

Authors

Hu H, Sun SC

Title

Ubiquitin signaling in immune responses.

Journal

Cell Res 26:457-83 (2016)
DOI:10.1038/cr.2016.40

Reference

Authors

Guo H, Callaway JB, Ting JP

Title

Inflammasomes: mechanism of action, role in disease, and therapeutics.

Journal

Nat Med 21:677-87 (2015)
DOI:10.1038/nm.3893

Reference

Authors

Man SM, Kanneganti TD

Title

Gasdermin D: the long-awaited executioner of pyroptosis.

Journal

Cell Res 25:1183-4 (2015)
DOI:10.1038/cr.2015.124

Reference

Authors

Rathinam VA, Vanaja SK, Waggoner L, Sokolovska A, Becker C, Stuart LM, Leong JM, Fitzgerald KA

Title

TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria.

Journal

Cell 150:606-19 (2012)
DOI:10.1016/j.cell.2012.07.007

Reference

Authors

Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S, Otageri P, Chandran B

Title

IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection.

Journal

Cell Host Microbe 9:363-75 (2011)
DOI:10.1016/j.chom.2011.04.008

Reference

Authors

Heilig R, Broz P

Title

Function and mechanism of the pyrin inflammasome.

Journal

Eur J Immunol 48:230-238 (2018)
DOI:10.1002/eji.201746947

Reference

Authors

Chakrabarti A, Banerjee S, Franchi L, Loo YM, Gale M Jr, Nunez G, Silverman RH

Title

RNase L activates the NLRP3 inflammasome during viral infections.

Journal

Cell Host Microbe 17:466-77 (2015)
DOI:10.1016/j.chom.2015.02.010

Related
pathway

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