KEGG   PATHWAY: hsa04621Help
Entry
hsa04621                    Pathway                                

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
NOD-like receptor signaling pathway
hsa04621

All organismsOrtholog table
Disease
H00282  
Cryopyrin associated periodic syndrome (CAPS)
H00285  
Blau syndrome
H00286  
Crohn's disease
H00287  
Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome
H00288  
Familial Mediterranean fever (FMF)
H00882  
Cocoon syndrome
H01109  
Chronic mucocutaneous candidiasis (CMC)
H01309  
Sarcoidosis, early-onset
H01372  
Vitiligo
H01744  
Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis
H01746  
STING-associated basculopathy with onset in infancy (SAVI)
H01748  
Autoinflammation with infantile enterocolitis (AIFEC)
Drug
D06635  
Rilonacept (USAN/INN)
D08978  
Pralnacasan (USAN/INN)
D09315  
Canakinumab (USAN/INN)
D09375  
Retaspimycin (USAN/INN)
D09376  
Retaspimycin hydrochloride (USAN)
D09911  
Gevokizumab (USAN/INN)
D10416  
Belnacasan (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
10392  
NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727]
8767  
RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
8517  
IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [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]
3553  
IL1B; interleukin 1 beta [KO:K04519]
3606  
IL18; interleukin 18 [KO:K05482]
3569  
IL6; interleukin 6 [KO:K05405]
7124  
TNF; tumor necrosis factor [KO:K03156]
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]
6885  
MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
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 and MAP3K7 binding protein 3 [KO:K12793]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
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]
3725  
JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
55054  
ATG16L1; autophagy related 16 like 1 [KO:K17890]
9474  
ATG5; autophagy related 5 [KO:K08339]
9140  
ATG12; autophagy related 12 [KO:K08336]
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]
10616  
RBCK1; RANBP2-type and C3HC4-type zinc finger containing 1 [KO:K10630] [EC:2.3.2.27]
55072  
RNF31; ring finger protein 31 [KO:K11974] [EC:2.3.2.27]
331  
XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
84674  
CARD6; caspase recruitment domain family member 6 [KO:K12797]
7205  
TRIP6; thyroid hormone receptor interactor 6 [KO:K12792]
55914  
ERBIN; erbb2 interacting protein [KO:K12796]
329  
BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
330  
BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
7186  
TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
7188  
TRAF5; TNF receptor associated factor 5 [KO:K09849]
7189  
TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
64170  
CARD9; caspase recruitment domain family member 9 [KO:K12794]
7128  
TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:3.4.19.12]
57506  
MAVS; mitochondrial antiviral signaling protein [KO:K12648]
7187  
TRAF3; TNF receptor associated factor 3 [KO:K03174]
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]
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]
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]
79671  
NLRX1; NLR family member X1 [KO:K12653]
118429  
ANTXR2; anthrax toxin receptor 2 [KO:K20909]
84168  
ANTXR1; anthrax toxin receptor 1 [KO:K20909]
22861  
NLRP1; NLR family pyrin domain containing 1 [KO:K12798]
29108  
PYCARD; PYD and CARD domain containing [KO:K12799]
834  
CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
596  
BCL2; BCL2, apoptosis regulator [KO:K02161]
598  
BCL2L1; BCL2 like 1 [KO:K04570]
1508  
CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
114548  
NLRP3; NLR family pyrin domain containing 3 [KO:K12800]
24145  
PANX1; pannexin 1 [KO:K03443]
5027  
P2RX7; purinergic receptor P2X 7 [KO:K05220]
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]
23236  
PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
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]
90550  
MCU; mitochondrial calcium uniporter [KO:K20858]
4938  
OAS1; 2'-5'-oligoadenylate synthetase 1 [KO:K14216] [EC:2.7.7.84]
4939  
OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
4940  
OAS3; 2'-5'-oligoadenylate synthetase 3 [KO:K14216] [EC:2.7.7.84]
6041  
RNASEL; ribonuclease L [KO:K01165]
56919  
DHX33; DEAH-box helicase 33 [KO:K17820] [EC:3.6.4.13]
55669  
MFN1; mitofusin 1 [KO:K21356] [EC:3.6.5.-]
9927  
MFN2; mitofusin 2 [KO:K06030] [EC:3.6.5.-]
8737  
RIPK1; receptor 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]
10059  
DNM1L; dynamin 1 like [KO:K17065] [EC:3.6.5.5]
10135  
NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
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]
7295  
TXN; thioredoxin [KO:K03671]
25828  
TXN2; thioredoxin 2 [KO:K03671]
140609  
NEK7; NIMA related kinase 7 [KO:K20876] [EC:2.7.11.1]
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]
260434  
PYDC1; pyrin domain containing 1 [KO:K12802]
152138  
PYDC2; pyrin domain containing 2 [KO:K20911]
4210  
MEFV; MEFV, pyrin innate immunity regulator [KO:K12803]
9051  
PSTPIP1; proline-serine-threonine phosphatase interacting protein 1 [KO:K12804]
841  
CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
8772  
FADD; Fas associated via death domain [KO:K02373]
CASP12; caspase 12 (gene/pseudogene) [KO:K04741] [EC:3.4.22.-]
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]
5580  
PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
2634  
GBP2; guanylate binding protein 2 [KO:K20897]
115362  
GBP5; guanylate binding protein 5 [KO:K20898]
9447  
AIM2; absent in melanoma 2 [KO:K12966]
3428  
IFI16; interferon gamma inducible protein 16 [KO:K20914]
7158  
TP53BP1; tumor protein p53 binding protein 1 [KO:K20915]
POP3; pyrin domain-only protein 3 [KO:K20916]
387  
RHOA; ras homolog family member A [KO:K04513]
2633  
GBP1; guanylate binding protein 1 [KO:K20899]
2635  
GBP3; guanylate binding protein 3 [KO:K20899]
115361  
GBP4; guanylate binding protein 4 [KO:K20899]
388646  
GBP7; guanylate binding protein 7 [KO:K20899]
837  
CASP4; caspase 4 [KO:K04394] [EC:3.4.22.57]
838  
CASP5; caspase 5 [KO:K04395] [EC:3.4.22.58]
79792  
GSDMD; gasdermin D [KO:K20917]
3454  
IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
3455  
IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
3716  
JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
7297  
TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
6772  
STAT1; signal transducer and activator of transcription 1 [KO:K11220]
6773  
STAT2; signal transducer and activator of transcription 2 [KO:K11221]
10379  
IRF9; interferon regulatory factor 9 [KO:K04693]
7099  
TLR4; toll like receptor 4 [KO:K10160]
148022  
TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
4615  
MYD88; myeloid differentiation primary response 88 [KO:K04729]
51135  
IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
340061  
TMEM173; transmembrane protein 173 [KO:K12654]
Compound
C00002  
ATP
C00076  
Calcium cation
C00155  
L-Homocysteine
C00238  
Potassium cation
C00533  
Nitric oxide
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C16054  
Defensin alpha-1
C16055  
Defensin alpha-2
C16056  
Defensin alpha-3
C16057  
Defensin alpha-4
C16058  
Defensin alpha-5
C16059  
Defensin beta-1
C16060  
Defensin beta-2
C16061  
Defensin beta-3
C16062  
Defensin beta-4
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
KO pathway
 

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