Entry
Name
NOD-like receptor signaling pathway - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
hsa04621 NOD-like receptor signaling pathway
Ortholog table
Network
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
N01567 NLRP1 inflammasome signaling pathway
N01568 Regulation of NLRP3 inflammasome signaling pathway, NLRP3 inhibition
N01569 NALP12 inflammasome signaling pathway
N01570 Regulation of Pyrin inflammasome signaling pathway, PSTPIP1
Drug
D03505 Cinacalcet hydrochloride (JAN/USAN)
D10676 Etelcalcetide (USAN/INN)
D10677 Etelcalcetide hydrochloride (JAN/USAN)
D11385 Inarigivir soproxil (USAN)
D11564 Upacicalcet sodium hydrate (JAN)
D11817 Deucravacitinib (JAN/USAN)
D12352 Eclitasertib (USAN/INN)
D12412 Emavusertib hydrochloride (USAN)
D12423 Selnoflast potassium (USAN)
D12532 Emavusertib mesylate (USAN)
D12533 Emavusertib maleate (USAN)
D12538 Emavusertib phosphate (USAN)
D12539 emavusertib tosylate (USAN)
D12575 Povorcitinib (USAN/INN)
D12576 Povorcitinib phosphate (USAN)
D12917 Upacicalcet sodium (USAN)
Organism
Homo sapiens (human) [GN:
hsa ]
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 ]
440738 MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435 ]
81631 MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435 ]
84557 MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435 ]
643246 MAP1LC3B2; microtubule associated protein 1 light chain 3 beta 2 [KO:K10435 ]
392288 MAP1LC3BP1; microtubule associated protein 1 light chain 3 beta pseudogene 1 [KO:K10435 ]
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 ]
63940 GPSM3; G protein signaling modulator 3 [KO:K15838 ]
345611 IRGM; immunity related GTPase M [KO:K14139 ] [EC:3.6.5.-]
4210 MEFV; MEFV innate immunity 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 ]
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; TIR domain containing 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 ]
Compound
C01245 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
Reference
Authors
Strober W, Murray PJ, Kitani A, Watanabe T
Title
Signalling pathways and molecular interactions of NOD1 and NOD2.
Journal
Reference
Authors
Estornes Y, Bertrand MJ
Title
IAPs, regulators of innate immunity and inflammation.
Journal
Reference
Authors
Jakopin Z
Title
Nucleotide-binding oligomerization domain (NOD) inhibitors: a rational approach toward inhibition of NOD signaling pathway.
Journal
Reference
Authors
Caruso R, Warner N, Inohara N, Nunez G
Title
NOD1 and NOD2: signaling, host defense, and inflammatory disease.
Journal
Reference
Authors
Murray PJ
Title
Beyond peptidoglycan for Nod2.
Journal
Reference
Authors
Lecat A, Piette J, Legrand-Poels S
Title
The protein Nod2: an innate receptor more complex than previously assumed.
Journal
Reference
Authors
Man SM, Kanneganti TD
Title
Converging roles of caspases in inflammasome activation, cell death and innate immunity.
Journal
Reference
Authors
Broz P, Dixit VM
Title
Inflammasomes: mechanism of assembly, regulation and signalling.
Journal
Reference
Authors
Man SM, Kanneganti TD
Title
Regulation of inflammasome activation.
Journal
Reference
Authors
Jo EK, Kim JK, Shin DM, Sasakawa C
Title
Molecular mechanisms regulating NLRP3 inflammasome activation.
Journal
Reference
Authors
Broz P, Monack DM
Title
Newly described pattern recognition receptors team up against intracellular pathogens.
Journal
Reference
Authors
Rathinam VA, Vanaja SK, Fitzgerald KA
Title
Regulation of inflammasome signaling.
Journal
Reference
Authors
Sutterwala FS, Haasken S, Cassel SL
Title
Mechanism of NLRP3 inflammasome activation.
Journal
Reference
Authors
Latz E, Xiao TS, Stutz A
Title
Activation and regulation of the inflammasomes.
Journal
Reference
Authors
Blander JM
Title
A long-awaited merger of the pathways mediating host defence and programmed cell death.
Journal
Reference
Authors
von Moltke J, Ayres JS, Kofoed EM, Chavarria-Smith J, Vance RE
Title
Recognition of bacteria by inflammasomes.
Journal
Reference
Authors
Abais JM, Xia M, Zhang Y, Boini KM, Li PL
Title
Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector?
Journal
Reference
Authors
Storek KM, Monack DM
Title
Bacterial recognition pathways that lead to inflammasome activation.
Journal
Reference
Authors
Hu H, Sun SC
Title
Ubiquitin signaling in immune responses.
Journal
Reference
Authors
Guo H, Callaway JB, Ting JP
Title
Inflammasomes: mechanism of action, role in disease, and therapeutics.
Journal
Reference
Authors
Man SM, Kanneganti TD
Title
Gasdermin D: the long-awaited executioner of pyroptosis.
Journal
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
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
Reference
Authors
Heilig R, Broz P
Title
Function and mechanism of the pyrin inflammasome.
Journal
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
Related pathway
hsa04620 Toll-like receptor signaling pathway
KO pathway