Entry |
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Name |
NOD-like receptor signaling pathway - Homo sapiens (human)
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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.
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Class |
Organismal Systems; Immune system
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Pathway map |
hsa04621 | NOD-like receptor signaling pathway |

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Network |
nt06137 OAS/RNase L pathway (viruses) nt06139 NLR signaling (viruses and bacteria) nt06163 Hepatitis C virus (HCV) nt06168 Herpes simplex virus 1 (HSV-1) nt06170 Influenza A virus (IAV) nt06263 Hepatocellular carcinoma |
Element |
N00515 | Oligoadenylate synthetase (OAS)/RNase L pathway |
N00742 | NLRP3 Inflammasome signaling pathway |
N00867 | NLRC4 Inflammasome signaling pathway |
N00868 | Pyrin Inflammasome signaling pathway |
N00934 | Non-canonical inflammasome signaling pathway |
N00940 | NOD-NFKB signaling pathway |
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Disease |
H00282 | Cryopyrin associated periodic syndrome |
H00287 | Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome |
H00288 | Familial Mediterranean fever |
H00289 | Recurrent hydatidiform moles |
H01109 | Chronic mucocutaneous candidiasis |
H01309 | Sarcoidosis, early-onset |
H01744 | Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis |
H01746 | STING-associated vasculopathy with onset in infancy |
H01748 | Autoinflammation with infantile enterocolitis |
H01900 | Encephalopathy due to defective mitochondrial and peroxisomal fission |
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Drug |
D03505 | Cinacalcet hydrochloride (JAN/USAN) |
D10676 | Etelcalcetide (USAN/INN) |
D10677 | Etelcalcetide hydrochloride (JAN/USAN) |
D11385 | Inarigivir soproxil (USAN) |
D11564 | Upacicalcet sodium hydrate (JAN) |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
10392 | NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727] |
8517 | IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210] |
1147 | CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10] |
4790 | NFKB1; nuclear factor kappa B subunit 1 [KO:K02580] |
5970 | RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735] |
3576 | CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030] |
2919 | CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505] |
2920 | CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505] |
2921 | CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505] |
6347 | CCL2; C-C motif chemokine ligand 2 [KO:K14624] |
6352 | CCL5; C-C motif chemokine ligand 5 [KO:K12499] |
820 | CAMP; cathelicidin antimicrobial peptide [KO:K13916] |
64127 | NOD2; nucleotide binding oligomerization domain containing 2 [KO:K10165] |
10454 | TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403] |
23118 | TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404] |
257397 | TAB3; TGF-beta activated kinase 1 (MAP3K7) binding protein 3 [KO:K12793] |
3725 | JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448] |
11337 | GABARAP; GABA type A receptor-associated protein [KO:K08341] |
23710 | GABARAPL1; GABA type A receptor associated protein like 1 [KO:K08341] |
11345 | GABARAPL2; GABA type A receptor associated protein like 2 [KO:K08341] |
10910 | SUGT1; SGT1 homolog, MIS12 kinetochore complex assembly cochaperone [KO:K12795] |
81858 | SHARPIN; SHANK associated RH domain interactor [KO:K20894] |
84674 | CARD6; caspase recruitment domain family member 6 [KO:K12797] |
7205 | TRIP6; thyroid hormone receptor interactor 6 [KO:K12792] |
329 | BIRC2; baculoviral IAP repeat containing 2 [KO:K16060] |
330 | BIRC3; baculoviral IAP repeat containing 3 [KO:K16060] |
7188 | TRAF5; TNF receptor associated factor 5 [KO:K09849] |
64170 | CARD9; caspase recruitment domain family member 9 [KO:K12794] |
57506 | MAVS; mitochondrial antiviral signaling protein [KO:K12648] |
7187 | TRAF3; TNF receptor associated factor 3 [KO:K03174] |
9641 | IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10] |
10010 | TANK; TRAF family member associated NFKB activator [KO:K12650] |
3661 | IRF3; interferon regulatory factor 3 [KO:K05411] |
3665 | IRF7; interferon regulatory factor 7 [KO:K09447] |
84168 | ANTXR1; ANTXR cell adhesion molecule 1 [KO:K20909] |
22861 | NLRP1; NLR family pyrin domain containing 1 [KO:K12798] |
29108 | PYCARD; PYD and CARD domain containing [KO:K12799] |
596 | BCL2; BCL2 apoptosis regulator [KO:K02161] |
114548 | NLRP3; NLR family pyrin domain containing 3 [KO:K12800] |
7226 | TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13] |
54822 | TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1] |
51393 | TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971] |
846 | CASR; calcium sensing receptor [KO:K04612] |
222545 | GPRC6A; G protein-coupled receptor class C group 6 member A [KO:K04622] |
3708 | ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958] |
3709 | ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959] |
3710 | ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960] |
7416 | VDAC1; voltage dependent anion channel 1 [KO:K05862] |
7417 | VDAC2; voltage dependent anion channel 2 [KO:K15040] |
7419 | VDAC3; voltage dependent anion channel 3 [KO:K15041] |
1536 | CYBB; cytochrome b-245 beta chain [KO:K21421] [EC:1.-.-.-] |
1535 | CYBA; cytochrome b-245 alpha chain [KO:K08009] |
10628 | TXNIP; thioredoxin interacting protein [KO:K20910] |
79184 | BRCC3; BRCA1/BRCA2-containing complex subunit 3 [KO:K11864] [EC:3.4.19.-] |
3320 | HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079] |
3326 | HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079] |
22900 | CARD8; caspase recruitment domain family member 8 [KO:K12801] |
4210 | MEFV; MEFV innate immuity regulator, pyrin [KO:K12803] |
9051 | PSTPIP1; proline-serine-threonine phosphatase interacting protein 1 [KO:K12804] |
8772 | FADD; Fas associated via death domain [KO:K02373] |
59082 | CARD18; caspase recruitment domain family member 18 [KO:K12806] |
440068 | CARD17; caspase recruitment domain family member 17 [KO:K12806] |
114769 | CARD16; caspase recruitment domain family member 16 [KO:K12806] |
171389 | NLRP6; NLR family pyrin domain containing 6 [KO:K20863] |
199713 | NLRP7; NLR family pyrin domain containing 7 [KO:K20864] |
91662 | NLRP12; NLR family pyrin domain containing 12 [KO:K20865] |
4671 | NAIP; NLR family apoptosis inhibitory protein [KO:K12807] |
58484 | NLRC4; NLR family CARD domain containing 4 [KO:K12805] |
2634 | GBP2; guanylate binding protein 2 [KO:K20897] |
3428 | IFI16; interferon gamma inducible protein 16 [KO:K20914] |
7158 | TP53BP1; tumor protein p53 binding protein 1 [KO:K20915] |
387 | RHOA; ras homolog family member A [KO:K04513] |
7531 | YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630] |
2633 | GBP1; guanylate binding protein 1 [KO:K20899] |
2635 | GBP3; guanylate binding protein 3 [KO:K20899] |
3454 | IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130] |
3455 | IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131] |
6772 | STAT1; signal transducer and activator of transcription 1 [KO:K11220] |
6773 | STAT2; signal transducer and activator of transcription 2 [KO:K11221] |
148022 | TICAM1; toll like receptor adaptor molecule 1 [KO:K05842] |
4615 | MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729] |
340061 | STING1; stimulator of interferon response cGAMP interactor 1 [KO:K12654] |
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Compound |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
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Reference |
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Authors |
Vandenabeele P, Bertrand MJ |
Title |
The role of the IAP E3 ubiquitin ligases in regulating pattern-recognition receptor signalling. |
Journal |
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Reference |
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Authors |
Strober W, Murray PJ, Kitani A, Watanabe T |
Title |
Signalling pathways and molecular interactions of NOD1 and NOD2. |
Journal |
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Reference |
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Authors |
Estornes Y, Bertrand MJ |
Title |
IAPs, regulators of innate immunity and inflammation. |
Journal |
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Reference |
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Authors |
Jakopin Z |
Title |
Nucleotide-binding oligomerization domain (NOD) inhibitors: a rational approach toward inhibition of NOD signaling pathway. |
Journal |
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Reference |
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Authors |
Caruso R, Warner N, Inohara N, Nunez G |
Title |
NOD1 and NOD2: signaling, host defense, and inflammatory disease. |
Journal |
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Reference |
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Authors |
Murray PJ |
Title |
Beyond peptidoglycan for Nod2. |
Journal |
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Reference |
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Authors |
Lecat A, Piette J, Legrand-Poels S |
Title |
The protein Nod2: an innate receptor more complex than previously assumed. |
Journal |
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Reference |
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Authors |
Man SM, Kanneganti TD |
Title |
Converging roles of caspases in inflammasome activation, cell death and innate immunity. |
Journal |
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Reference |
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Authors |
Broz P, Dixit VM |
Title |
Inflammasomes: mechanism of assembly, regulation and signalling. |
Journal |
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Reference |
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Authors |
Man SM, Kanneganti TD |
Title |
Regulation of inflammasome activation. |
Journal |
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Reference |
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Authors |
Jo EK, Kim JK, Shin DM, Sasakawa C |
Title |
Molecular mechanisms regulating NLRP3 inflammasome activation. |
Journal |
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Reference |
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Authors |
Broz P, Monack DM |
Title |
Newly described pattern recognition receptors team up against intracellular pathogens. |
Journal |
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Reference |
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Authors |
Rathinam VA, Vanaja SK, Fitzgerald KA |
Title |
Regulation of inflammasome signaling. |
Journal |
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Reference |
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Authors |
Sutterwala FS, Haasken S, Cassel SL |
Title |
Mechanism of NLRP3 inflammasome activation. |
Journal |
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Reference |
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Authors |
Latz E, Xiao TS, Stutz A |
Title |
Activation and regulation of the inflammasomes. |
Journal |
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Reference |
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Authors |
Blander JM |
Title |
A long-awaited merger of the pathways mediating host defence and programmed cell death. |
Journal |
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Reference |
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Authors |
von Moltke J, Ayres JS, Kofoed EM, Chavarria-Smith J, Vance RE |
Title |
Recognition of bacteria by inflammasomes. |
Journal |
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Reference |
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Authors |
Abais JM, Xia M, Zhang Y, Boini KM, Li PL |
Title |
Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? |
Journal |
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Reference |
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Authors |
Storek KM, Monack DM |
Title |
Bacterial recognition pathways that lead to inflammasome activation. |
Journal |
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Reference |
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Authors |
Hu H, Sun SC |
Title |
Ubiquitin signaling in immune responses. |
Journal |
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Reference |
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Authors |
Guo H, Callaway JB, Ting JP |
Title |
Inflammasomes: mechanism of action, role in disease, and therapeutics. |
Journal |
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Reference |
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Authors |
Man SM, Kanneganti TD |
Title |
Gasdermin D: the long-awaited executioner of pyroptosis. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Heilig R, Broz P |
Title |
Function and mechanism of the pyrin inflammasome. |
Journal |
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Related pathway |
hsa04620 | Toll-like receptor signaling pathway |
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KO pathway |
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