IL18 signaling (Homo sapiens)

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CYNUIRAK1P1IL-18 Signaling PathwayCYCSTRAF6IL18RAPIL18BAXIL18R1MAPK1Y204IL-18BPProteinProtein - protein dissociationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation Induced catalysisProtein-protein interactionLEGENDPhosphorylationGolgi apparatusEndosomeNucleusMitochondrionCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageProteinmRNALigandEnzyme complexCASP8NOX1TICAM2SLC12A3LCKPCYMTCYCSCYMTNFKB1NCF1NCF2NCF1NCF2CYPMIMP3ELAVL1CTNNB1GSK3BCYNUCCL2CCL3CCL4IL18R1IL18RAPIL18BPIFNGMMP3MMP8MMP14MMP13MMP9MMP2LTBIL13TIMP3TIMP1PTX3IER3TP53MYH6IL17RCIL18TRPM7DEKFOXN3PRCCHSPB8CCL5BTG2TNIP3CCL1TMEM165BIN1TSHZ1MBTPS1PTPN7PHF20TRPC2MTCH1HPS1SLC4A7AARSUCK1ZNF219NSMFKCNH2PPP1R13LPLOD3MEPCEARFGAP2RASA3TRPC4APPTMSEEF2ProteinInduced activationInterleukinsChemokinesMatrix metalloproteases CytokinesCDsTNF familyGrowth factorsTight-junctionproteinsTranscriptionfactorsCell cycleregulatorsOxidativestressMetabolic enzymesTransport proteinsNFKB familyUncategorizedCell deathregulatorsStructural proteinsOthersHormonesPhosphatasesKinasesDeacetylases and UbiquitinasesProtein-modifying enzymesTRAF1FASFADDTNFSF11TNFRSF11BTNFAIP2TNFAIP3TNFFASLGCLDN12CLDN4CLDN3CLDN1CLDN15Signaling proteinsProteinsynthesisJUNRUNX2FOSIRF6KLF2BIRC3BADBCL2BCL2L1PTENPTPRZ1CCNB2CCNA2CDK5R2mRNAsplicingPLA2G7NACAEPB41SYT10ZNF444RUSC1CCDC9FAM110AITM2CGRNATF3NFKBIANFKBIERELBNFKB2RELNFKB1RELANFKBIZAKT1S473T308MAPK3T202CREB1S133MAPK14T180Y182PIK3R1PELK1S383MAPK8T183Y185ATF2T71CHUKPIKBKBPRPS6S240S244S235S236SRCY419Y139NFKBIAPHSPB1PCSN2PMAP3K7PGSK3AS21PTENPACACBS79JUNS63S73GRIN2BPPRKCAPPRKCBPRAF1Y360Y361TNFRSF1AMEF2ACEBPBGATA1SP1CFLARBIDCASP3IRF1TNFTP53FASLGFASCYPMMAPK9T180Y182ProteinInduced inhibitionReceptorNUCLEUSCYTOPLASMPLASMAMEMBRANEMITOCHONDRIAMYD88IL1BIL2RAIL10IL12BIL9IL6CCL19CCL20CXCL16CXCL2CXCL3CCL18CXCL8MMP1NR1H3ABHD16ATACR1SDC4RGS16SOCS3EPS8GRM7NR4A1SEMA6DHCAR2SEMA6CARF6RXRBRPTORS1PR4CD36CD83CD81VEGFACCN4BMP2HDGFNOS2LONP2ELAVL1IMP3NFATC4S676NFKB1RELAS536S276CTNNB1GSK3BS9CYNUCYNUCYNUCYNUCYNUNFATC4BSGFN1CNTN2ICAM1SPP1ITGA2BCell adhesionmoleculesRELACOL1A1COL3A1COL1A2DESMYH7ACTA1TMSB4XACTA2SNTB1CRYGCLMNB2KLC1Ion channelsTFCETPRAE1B2MABCF1ARL4DTOMM40RANGAP1PKN1KITLGBAZ1BSTK40HDAC3USP5FBXW7ADIPOQNR0B2NDUFC1ZDHHC7GPAT4HMOX1ENO1UGGT1PYGBLARS2PLCG1APBA2ADAMTS5STOML1ZC3H12AZNF143FAM186BNRN1SPON1STMN1RPS11NPPBNPPAKRT31FUT1CA11ANP32ALRRFIP1NCAPH2ZBTB7ARND2ALS2ARFGAP1PRM1KIFC3PWWP3ACENPBHOXD8BPGMACADSCPT1AHADHPTGS2PPT2ACOD1COX17ECH1TGM2PLD1PIGTUGT2B10ARG1IRAK4MAP2K7STAT3Y705BAXAMPK1T172PARP1RPS6KB1T389IL37ULBP2MYD88RFX5TBX21STAT3CYNUPRKCDPBADS136Promotes Th1 responseActivation of intrinsic and extrinsic proapoptotic signalingImmune process proteinsInduces NK cellsand Th1 responsePro-apoptoticreponseMucosal mast cellinduced Th2 responseMucosal mast cell differentiationMucosal mast cell induced Th2 responseinduces ECM degradation andcardiac remodelingMMP inhibitorsAugments liver cellproliferationInduces inflammatory responseRegulates NK cell activity during Listeria infectionIncreases intestinalhyperpermeabilityand microbial translocationEnhances breast cancer cell migration


Description

Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated T-helper (Th)1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through its binding to the IL-18 receptor complex and activation of nuclear factor-κB (NF-κB), culminating in the production and release of several cytokines, chemokines, and cellular adhesion molecules. In certain cell types, IL-18 also activates mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase/ AKT serine/threonine kinase (PI3K/AKT) signaling modules leading to the production and release of proinflammatory cytokines. IL-18-mediated signaling acts as one of the vital components of the immunomodulatory cytokine networks involved in host defense, inflammation, and tissue regeneration. Albeit its biomedical importance, a comprehensive resource of IL-18 mediated signaling pathway is currently lacking. In this study, we report on the development of an integrated pathway map of IL-18/IL-18R signaling. The pathway map was developed through literature mining from published literature based on manual curation guidelines adapted from NetPath and includes information on 16 protein-protein interaction events, 38 enzyme-catalysis events, 12 protein translocation events, 26 activations/inhibition events, transcriptional regulators, 230 gene regulation events and 84 induced protein expression events.

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Bibliography

  1. Rex DAB, Agarwal N, Prasad TSK, Kandasamy RK, Subbannayya Y, Pinto SM; ''A comprehensive pathway map of IL-18-mediated signalling.''; J Cell Commun Signal, 2019 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
129677view00:45, 22 May 2024EweitzModified title
126321view05:20, 21 April 2023EgonwLicense is CCZero
115147view06:57, 29 January 2021Rex D A BModified title
110011view18:31, 12 April 2020EgonwFixed the data source for NCBI Protein identifiers.
108627view18:33, 13 January 2020Khanspersconverted interactions to graphical lines in legend
108624view11:00, 13 January 2020Subbannayyaadded literature reference
108623view10:57, 13 January 2020SubbannayyaModified description
108059view10:24, 27 November 2019SubbannayyaNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AARSRna16 (Entrez Gene)
ABCF1Rna23 (Entrez Gene)
ABHD16A Rna7920 (Entrez Gene)
ACACBGeneProduct32 (Entrez Gene)
ACADS Rna35 (Entrez Gene)
ACOD1 Rna730249 (Entrez Gene)
ACTA1Rna58 (Entrez Gene)
ACTA2Rna59 (Entrez Gene)
ADAMTS5 Rna11096 (Entrez Gene)
ADIPOQRna9370 (Entrez Gene)
AKT1GeneProductNP_005154.2 (NCBI Protein)
ALS2 Rna57679 (Entrez Gene)
AMPK1GeneProduct5562 (Entrez Gene)
ANP32ARna8125 (Entrez Gene)
APBA2Rna321 (Entrez Gene)
ARF6Rna382 (Entrez Gene)
ARFGAP1 Rna55738 (Entrez Gene)
ARFGAP2Rna84364 (Entrez Gene)
ARG1 Rna383 (Entrez Gene)
ARL4DRna379 (Entrez Gene)
ATF2 Rna467 (Entrez Gene)
ATF3 Rna467 (Entrez Gene)
B2MRna567 (Entrez Gene)
BADRna572 (Entrez Gene)
BAXGeneProduct581 (Entrez Gene)
BAZ1BRna9031 (Entrez Gene)
BCL2Rna596 (Entrez Gene)
BCL2L1Rna598 (Entrez Gene)
BIDGeneProduct637 (Entrez Gene)
BIN1Rna274 (Entrez Gene)
BIRC3Rna330 (Entrez Gene)
BMP2 Rna650 (Entrez Gene)
BPGMRna669 (Entrez Gene)
BSGRna682 (Entrez Gene)
BTG2 Rna7832 (Entrez Gene)
CA11Rna770 (Entrez Gene)
CASP3GeneProduct836 (Entrez Gene)
CASP8GeneProduct841 (Entrez Gene)
CCDC9Rna26093 (Entrez Gene)
CCL1Rna6346 (Entrez Gene)
CCL18Rna6362 (Entrez Gene)
CCL19Rna6363 (Entrez Gene)
CCL20Rna6364 (Entrez Gene)
CCL2Rna6347 (Entrez Gene)
CCL3Rna6348 (Entrez Gene)
CCL4Rna6351 (Entrez Gene)
CCL5Rna6352 (Entrez Gene)
CCN4 Rna8840 (Entrez Gene)
CCNA2 Rna890 (Entrez Gene)
CCNB2 Rna9133 (Entrez Gene)
CD36Rna948 (Entrez Gene)
CD81 Rna975 (Entrez Gene)
CD83Rna9308 (Entrez Gene)
CDK5R2Rna8941 (Entrez Gene)
CEBPBGeneProduct1051 (Entrez Gene)
CENPBRna1059 (Entrez Gene)
CETPRna1071 (Entrez Gene)
CFLARGeneProduct8837 (Entrez Gene)
CHUKGeneProduct1147 (Entrez Gene)
CLDN12 Rna9069 (Entrez Gene)
CLDN15 Rna24146 (Entrez Gene)
CLDN1Rna9076 (Entrez Gene)
CLDN3 Rna1365 (Entrez Gene)
CLDN4 Rna1364 (Entrez Gene)
CNTN2Rna6900 (Entrez Gene)
COL1A1Rna1277 (Entrez Gene)
COL1A2 Rna1278 (Entrez Gene)
COL3A1Rna1281 (Entrez Gene)
COX17 Rna10063 (Entrez Gene)
CPT1ARna1374 (Entrez Gene)
CREB1GeneProductNP_604391.1 (NCBI Protein)
CRYGCRna1420 (Entrez Gene)
CSN2GeneProduct1447 (Entrez Gene)
CTNNB1GeneProduct1499 (Entrez Gene)
CXCL16Rna58191 (Entrez Gene)
CXCL2 Rna2920 (Entrez Gene)
CXCL3 Rna2921 (Entrez Gene)
CXCL8Rna3576 (Entrez Gene)
CYCSGeneProduct54205 (Entrez Gene)
DEKRna7913 (Entrez Gene)
DESRna1674 (Entrez Gene)
ECH1 Rna1891 (Entrez Gene)
EEF2Rna1938 (Entrez Gene)
ELAVL1GeneProduct1994 (Entrez Gene)
ELK1GeneProductNP_001107595.1 (NCBI Protein)
ENO1Rna2023 (Entrez Gene)
EPB41Rna2035 (Entrez Gene)
EPS8Rna2059 (Entrez Gene)
FADD Rna8772 (Entrez Gene)
FAM110ARna83541 (Entrez Gene)
FAM186BRna84070 (Entrez Gene)
FASGeneProduct355 (Entrez Gene)
FASLGGeneProduct356 (Entrez Gene)
FBXW7Rna55294 (Entrez Gene)
FN1Rna2335 (Entrez Gene)
FOSRna2353 (Entrez Gene)
FOXN3Rna1112 (Entrez Gene)
FUT1 Rna2523 (Entrez Gene)
GATA1GeneProduct2623 (Entrez Gene)
GPAT4Rna137964 (Entrez Gene)
GRIN2BGeneProduct2904 (Entrez Gene)
GRM7Rna2917 (Entrez Gene)
GRNRna2896 (Entrez Gene)
GSK3AGeneProductNP_002084.2 (NCBI Protein)
GSK3BGeneProduct2932 (Entrez Gene)
HADH Rna3033 (Entrez Gene)
HCAR2Rna338442 (Entrez Gene)
HDAC3Rna8841 (Entrez Gene)
HDGF Rna3068 (Entrez Gene)
HMOX1Rna3162 (Entrez Gene)
HOXD8Rna3234 (Entrez Gene)
HPS1Rna3257 (Entrez Gene)
HSPB1GeneProduct3315 (Entrez Gene)
HSPB8 Rna26353 (Entrez Gene)
ICAM1 Rna3383 (Entrez Gene)
IER3Rna8870 (Entrez Gene)
IFNGRna3458 (Entrez Gene)
IKBKBGeneProduct3551 (Entrez Gene)
IL-18BPGeneProduct10068 (NCBI Protein)
IL10 Rna3586 (Entrez Gene)
IL12B Rna3593 (Entrez Gene)
IL13Rna3596 (Entrez Gene)
IL17RC Rna84818 (Entrez Gene)
IL18Rna3606 (Entrez Gene)
IL18BPRna10068 (Entrez Gene)
IL18R1Rna8809 (Entrez Gene)
IL18RAPRna8807 (Entrez Gene)
IL1BRna3553 (Entrez Gene)
IL2RARna3559 (Entrez Gene)
IL37Protein27178 (Entrez Gene)
IL6Rna3569 (Entrez Gene)
IL9 Rna3578 (Entrez Gene)
IMP3GeneProduct55272 (Entrez Gene)
IRAK1Protein3654 (Entrez Gene)
IRAK4GeneProduct12682231 (Entrez Gene)
IRF1GeneProduct3659 (Entrez Gene)
IRF6Rna3664 (Entrez Gene)
ITGA2BRna3674 (Entrez Gene)
ITM2CRna81618 (Entrez Gene)
JUNRna3725 (Entrez Gene)
JUNGeneProductNP_002219.1 (NCBI Protein)
KCNH2Rna3757 (Entrez Gene)
KIFC3Rna3801 (Entrez Gene)
KITLGRna4254 (Entrez Gene)
KLC1Rna3831 (Entrez Gene)
KLF2Rna10365 (Entrez Gene)
KRT31Rna3881 (Entrez Gene)
LARS2Rna23395 (Entrez Gene)
LCKGeneProduct3932 (Entrez Gene)
LMNB2Rna84823 (Entrez Gene)
LONP2Rna83752 (Entrez Gene)
LRRFIP1Rna9208 (Entrez Gene)
LTB Rna4050 (Entrez Gene)
MAP2K7GeneProduct5609 (Entrez Gene)
MAP3K7GeneProduct6885 (Entrez Gene)
MAPK14GeneProductNP_001306.1 (NCBI Protein)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MAPK8GeneProductNP_620637.1 (NCBI Protein)
MAPK9GeneProduct5601 (Entrez Gene)
MBTPS1 Rna8720 (Entrez Gene)
MEF2A GeneProduct4205 (Entrez Gene)
MEPCERna56257 (Entrez Gene)
MMP13 Rna4322 (Entrez Gene)
MMP1Rna4312 (Entrez Gene)
MMP14Rna4323 (Entrez Gene)
MMP2 Rna4313 (Entrez Gene)
MMP3Rna4314 (Entrez Gene)
MMP8 Rna4317 (Entrez Gene)
MMP9 Rna4318 (Entrez Gene)
MTCH1Rna23787 (Entrez Gene)
MYD88 Rna4615 (Entrez Gene)
MYD88Protein4615 (Entrez Gene)
MYH6 Rna4624 (Entrez Gene)
MYH7Rna4625 (Entrez Gene)
NACARna4666 (Entrez Gene)
NCAPH2Rna29781 (Entrez Gene)
NCF1GeneProduct653361 (Entrez Gene)
NCF2GeneProduct4688 (Entrez Gene)
NDUFC1Rna4717 (Entrez Gene)
NFATC4GeneProduct4776 (Entrez Gene)
NFKB1GeneProduct4790 (Entrez Gene)
NFKB2 Rna4791 (Entrez Gene)
NFKBIA Rna4792 (Entrez Gene)
NFKBIAGeneProduct4792 (Entrez Gene)
NFKBIE Rna4794 (Entrez Gene)
NFKBIZRna64332 (Entrez Gene)
NOS2 Rna4843 (Entrez Gene)
NOX1GeneProduct27035 (Entrez Gene)
NPPARna4878 (Entrez Gene)
NPPBRna4879 (Entrez Gene)
NR0B2Rna8431 (Entrez Gene)
NR1H3Rna10062 (Entrez Gene)
NR4A1 Rna3164 (Entrez Gene)
NRN1 Rna51299 (Entrez Gene)
NSMFRna26012 (Entrez Gene)
PARP1GeneProduct142 (Entrez Gene)
PHF20Rna51230 (Entrez Gene)
PIGTRna51604 (Entrez Gene)
PIK3R1GeneProduct5295 (Entrez Gene)
PKN1Rna5585 (Entrez Gene)
PLA2G7Rna7941 (Entrez Gene)
PLCG1Rna5335 (Entrez Gene)
PLD1Rna5337 (Entrez Gene)
PLOD3Rna8985 (Entrez Gene)
PPP1R13LRna10848 (Entrez Gene)
PPT2 Rna9374 (Entrez Gene)
PRCCRna5546 (Entrez Gene)
PRKCAGeneProduct5578 (Entrez Gene)
PRKCBGeneProduct5579 (Entrez Gene)
PRKCDGeneProduct5580 (Entrez Gene)
PRM1Rna5619 (Entrez Gene)
PTENGeneProduct5728 (Entrez Gene)
PTGS2Rna5743 (Entrez Gene)
PTMSRna5763 (Entrez Gene)
PTPN7 Rna5778 (Entrez Gene)
PTPRZ1Rna5803 (Entrez Gene)
PTX3Rna5806 (Entrez Gene)
PWWP3ARna84939 (Entrez Gene)
PYGBRna5834 (Entrez Gene)
ProteinGeneProduct11 (Entrez Gene)
RAE1 Rna8480 (Entrez Gene)
RAF1GeneProductNP_001341618.1 (NCBI Protein)
RANGAP1Rna5905 (Entrez Gene)
RASA3Rna22821 (Entrez Gene)
RELRna5966 (Entrez Gene)
RELA Rna5970 (Entrez Gene)
RELAGeneProduct5970 (Entrez Gene)
RELB Rna5966 (Entrez Gene)
RFX5 Rna5993 (Entrez Gene)
RGS16Rna6004 (Entrez Gene)
RND2 Rna8153 (Entrez Gene)
RPS11 Rna6205 (Entrez Gene)
RPS6KB1GeneProduct6198 (Entrez Gene)
RPS6GeneProductNP_001001.2 (NCBI Protein)
RPTORRna57521 (Entrez Gene)
RUNX2Rna860 (Entrez Gene)
RUSC1 Rna23623 (Entrez Gene)
RXRBRna6257 (Entrez Gene)
S1PR4 Rna8698 (Entrez Gene)
SDC4Rna6385 (Entrez Gene)
SEMA6C Rna10500 (Entrez Gene)
SEMA6DRna80031 (Entrez Gene)
SLC12A3GeneProduct6559 (Entrez Gene)
SLC4A7Rna9497 (Entrez Gene)
SNTB1 Rna6641 (Entrez Gene)
SOCS3 Rna9021 (Entrez Gene)
SP1GeneProduct6667 (Entrez Gene)
SPON1Rna10418 (Entrez Gene)
SPP1 Rna6696 (Entrez Gene)
SRCGeneProductNP_005408.1 (NCBI Protein)
STAT3GeneProductNP_644805.1 (NCBI Protein)
STK40Rna83931 (Entrez Gene)
STMN1 Rna3925 (Entrez Gene)
STOML1 Rna9399 (Entrez Gene)
SYT10Rna341359 (Entrez Gene)
TACR1 Rna6869 (Entrez Gene)
TBX21Rna30009 (Entrez Gene)
TFRna7018 (Entrez Gene)
TGM2Rna7052 (Entrez Gene)
TICAM2GeneProduct353376 (Entrez Gene)
TIMP1 Rna7076 (Entrez Gene)
TIMP3 Rna7078 (Entrez Gene)
TMEM165 Rna55858 (Entrez Gene)
TMSB4XRna7114 (Entrez Gene)
TNFGeneProduct7124 (Entrez Gene)
TNFAIP2 Rna7127 (Entrez Gene)
TNFAIP3 Rna7128 (Entrez Gene)
TNFRSF11B Rna4982 (Entrez Gene)
TNFRSF1AGeneProduct7132 (Entrez Gene)
TNFSF11Rna8600 (Entrez Gene)
TNIP3Rna79931 (Entrez Gene)
TOMM40Rna10452 (Entrez Gene)
TP53GeneProduct7157 (Entrez Gene)
TRAF1Rna7185 (Entrez Gene)
TRAF6Protein7189 (Entrez Gene)
TRPC2 Rna7221 (Entrez Gene)
TRPC4APRna26133 (Entrez Gene)
TRPM7 Rna54822 (Entrez Gene)
TSHZ1 Rna10194 (Entrez Gene)
UCK1Rna83549 (Entrez Gene)
UGGT1 Rna56886 (Entrez Gene)
UGT2B10 Rna7365 (Entrez Gene)
ULBP2Rna80328 (Entrez Gene)
USP5Rna8078 (Entrez Gene)
VEGFA Rna7422 (Entrez Gene)
ZBTB7ARna51341 (Entrez Gene)
ZC3H12ARna80149 (Entrez Gene)
ZDHHC7 Rna55625 (Entrez Gene)
ZNF143 Rna7702 (Entrez Gene)
ZNF219Rna51222 (Entrez Gene)
ZNF444Rna55311 (Entrez Gene)

Annotated Interactions

No annotated interactions

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