TUMOR NECROSIS FACTOR MEDIATED SIGNALING PATHWAY (PW:0000233)

View Ontology Report

Description

Tumor necrosis factor (Tnf or Tnfa) signaling pathway plays pivotal roles in immunity, cell proliferation, differentiation and apoptosis through the activation of several downstream signaling cascades. Tumor necrosis factor and its receptors Tnfrsf1a and Tnfrsf1b (Tnfr1 and Tnfr2) belong to the tumor necrosis superfamilies of ligands and receptors of which 19 and 29 members have been so far identified in humans, respectively. Tnf signaling occurs primarily via Tnfrsf1a receptor (Tnf-R1), ubiquit

Pathway Diagram:

Elsevier Inc. Ripk1 K63-ubiquitin M1-Ubiquitin Tradd M1-ubiquitination K63-ubiquitin ---- Tab3 K63-ubiquitin ---- Tab2 Cyld Casp8 ---- Fadd Fadd Casp8 --+> extrinsic apoptotic pathway extrinsic apoptotic pathway TRAF5 Traf2 Birc2 ---> Ripk1 Birc3 ---- Traf2 Birc3 Ripk1 --+> Map3k7 Birc3 ---- LUBAC complex Bag4 Fadd ---- Tradd Tnfrsf1a ---- Tradd Tnfrsf1a Adam17 ---> Tnf Tnf ---- Tnfrsf1a Tnf Bag4 ---| Tnfrsf1a Tradd ---- TRAF5 Tradd ---- Traf2 Ripk1 ---- Tradd Birc2 Birc2 ---- LUBAC complex LUBAC complex ---- TRAF5 LUBAC complex ---- Tradd LUBAC complex ---- Traf2 A20 ubiquitin-editing complex ---| K63-polyubiquitination Adam17 nuclear factor kappa B signaling pathway Map3k7 --+> nuclear factor kappa B signaling pathway p38 MAPK signaling pathway Map3k7 Map3k7 ---- Tab1 LUBAC complex ---> Ripk1 Birc3 ---> Ripk1 Map3k7 --+> p38 MAPK signaling pathway c-Jun N-terminal kinases MAPK signaling pathway Map3k7 --+> c-Jun N-terminal kinases MAPK signaling pathway Tab1 Tab2 Tab3 Casp8 Map3k7 ---- Tab3 Map3k7 ---- Tab2 A20 ubiquitin-editing complex LUBAC complex K63-polyubiquitination Cyld ---| Map3k7 Cyld ---| K63-polyubiquitination
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Genes in Pathway:

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tumor necrosis factor mediated signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Adam17 ADAM metallopeptidase domain 17 JBrowse link 6 43,400,525 43,448,280 RGD:2292150
RGD:6484113
G Bag4 BCL2-associated athanogene 4 JBrowse link 16 71,057,709 71,075,874 RGD:2292150
RGD:6484113
G Birc2 baculoviral IAP repeat-containing 2 JBrowse link 8 6,014,014 6,036,668 RGD:6484113
RGD:7800730
G Birc3 baculoviral IAP repeat-containing 3 JBrowse link 8 6,048,590 6,076,828 RGD:6484113
RGD:7800730
G Casp8 caspase 8 JBrowse link 9 65,614,142 65,662,624 RGD:6484113
G Cav1 caveolin 1 JBrowse link 4 44,597,123 44,630,206 RGD:6484113
G Chuk conserved helix-loop-helix ubiquitous kinase JBrowse link 1 263,848,829 263,884,354 RGD:2292150
RGD:6484113
G Cyld CYLD lysine 63 deubiquitinase JBrowse link 19 19,264,984 19,323,817 RGD:6484113
RGD:7800735
RGD:7800734
G Fadd Fas associated via death domain JBrowse link 1 217,746,176 217,748,581 RGD:2292150
RGD:6484113
G Ikbkb inhibitor of nuclear factor kappa B kinase subunit beta JBrowse link 16 74,177,233 74,230,809 RGD:2292150
RGD:6484113
G Ikbkg inhibitor of nuclear factor kappa B kinase subunit gamma JBrowse link X 156,254,187 156,280,046 RGD:2292150
RGD:6484113
G Itch itchy E3 ubiquitin protein ligase JBrowse link 3 150,660,665 150,752,016 RGD:7800734
RGD:7800735
G Madd MAP-kinase activating death domain JBrowse link 3 79,960,301 80,003,023 RGD:6484113
G Map2k3 mitogen activated protein kinase kinase 3 JBrowse link 10 45,089,455 45,110,802 RGD:6484113
G Map2k7 mitogen activated protein kinase kinase 7 JBrowse link 12 2,546,278 2,555,310 RGD:6484113
G Map3k1 mitogen-activated protein kinase kinase kinase 1 JBrowse link 2 43,329,516 43,393,203 RGD:6484113
G Map3k3 mitogen activated protein kinase kinase kinase 3 JBrowse link 10 94,280,703 94,349,372 RGD:6484113
G Map3k5 mitogen-activated protein kinase kinase kinase 5 JBrowse link 1 15,412,603 15,613,752 RGD:6484113
G Map3k7 mitogen activated protein kinase kinase kinase 7 JBrowse link 5 47,183,142 47,244,424 RGD:6484113
RGD:5490225
G Map4k2 mitogen activated protein kinase kinase kinase kinase 2 JBrowse link 1 221,710,622 221,726,274 RGD:6484113
G Map4k3 mitogen-activated protein kinase kinase kinase kinase 3 JBrowse link 6 3,276,732 3,444,519 RGD:6484113
G Map4k4 mitogen-activated protein kinase kinase kinase kinase 4 JBrowse link 9 46,657,444 46,782,545 RGD:6484113
G Map4k5 mitogen-activated protein kinase kinase kinase kinase 5 JBrowse link 6 92,136,242 92,229,578 RGD:6484113
G Nfkb1 nuclear factor kappa B subunit 1 JBrowse link 2 240,773,520 240,890,053 RGD:6484113
G Nrk Nik related kinase JBrowse link X
X
109,940,439
110,065,199
110,036,361
110,089,124
RGD:6484113
G Nsmaf neutral sphingomyelinase activation associated factor JBrowse link 5 19,499,111 19,560,308 RGD:6484113
G Prkci protein kinase C, iota JBrowse link 2 115,941,998 116,002,550 RGD:6484113
G Prkcz protein kinase C, zeta JBrowse link 5 172,658,071 172,769,492 RGD:6484113
G Rack1 receptor for activated C kinase 1 JBrowse link 10 34,149,717 34,155,198 RGD:6484113
G Rbck1 RANBP2-type and C3HC4-type zinc finger containing 1 JBrowse link 3 147,793,014 147,809,941 RGD:7800730
G Rela RELA proto-oncogene, NF-kB subunit JBrowse link 1 220,992,770 221,003,249 RGD:6484113
G Rffl ring finger and FYVE-like domain containing E3 ubiquitin protein ligase JBrowse link 10 70,157,621 70,220,618 RGD:6484113
G Ripk1 receptor interacting serine/threonine kinase 1 JBrowse link 17 31,537,580 31,569,904 RGD:2292150
RGD:7800730
RGD:6484113
G Rnf11 ring finger protein 11 JBrowse link 5 129,296,271 129,298,513 RGD:7800734
RGD:7800735
G Rnf31 ring finger protein 31 JBrowse link 15 34,270,037 34,282,385 RGD:7800730
G Sharpin SHANK-associated RH domain interactor JBrowse link 7 117,413,151 117,417,455 RGD:7800730
G Smpd1 sphingomyelin phosphodiesterase 1 JBrowse link 1 170,383,682 170,387,525 RGD:6484113
G Smpd2 sphingomyelin phosphodiesterase 2 JBrowse link 20 46,212,070 46,215,183 RGD:6484113
G Sqstm1 sequestosome 1 JBrowse link 10 35,704,728 35,716,316 RGD:6484113
G Stat1 signal transducer and activator of transcription 1 JBrowse link 9 54,287,540 54,327,958 RGD:6484113
G Tab1 TGF-beta activated kinase 1/MAP3K7 binding protein 1 JBrowse link 7 121,350,953 121,382,100 RGD:6484113
RGD:5490225
G Tab2 TGF-beta activated kinase 1/MAP3K7 binding protein 2 JBrowse link 1 1,999,574 2,017,574 RGD:6484113
RGD:5490225
G Tab3 TGF-beta activated kinase 1 and MAP3K7 binding protein 3 JBrowse link X 54,035,958 54,090,282 RGD:5490225
G Tax1bp1 Tax1 binding protein 1 JBrowse link 4 82,776,720 82,832,586 RGD:7800734
RGD:7800735
G Tnf tumor necrosis factor JBrowse link 20 5,189,382 5,192,000 RGD:1580210
RGD:6484113
RGD:2292150
G Tnfaip3 TNF alpha induced protein 3 JBrowse link 1 14,401,103 14,416,369 RGD:7800734
RGD:7800735
G Tnfrsf1a TNF receptor superfamily member 1A JBrowse link 4 157,864,905 157,877,634 RGD:2292150
RGD:6484113
RGD:5130945
G Tnfrsf1b TNF receptor superfamily member 1B JBrowse link 5 163,136,390 163,167,299 RGD:2292150
RGD:6484113
G Tnik TRAF2 and NCK interacting kinase JBrowse link 2 113,984,599 114,391,805 RGD:6484113
G Tradd TNFRSF1A-associated via death domain JBrowse link 19 37,214,461 37,221,099 RGD:2292150
RGD:6484113
G Traf2 Tnf receptor-associated factor 2 JBrowse link 3 2,746,061 2,770,690 RGD:2292150
RGD:7800730
RGD:6484113
RGD:5130945
G Txn1 thioredoxin 1 JBrowse link 5 75,049,735 75,057,731 RGD:6484113

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
ComplexA10 ubiqutin-editing complexdeubiquitinase, K48-ubiquitin
ComplexLUBAC complexM1-ubiquitin

Pathway Gene Annotations

Pathway Annotations Associated with Genes in the tumor necrosis factor mediated signaling pathway
Pathway TermsGene Symbols
acute myeloid leukemia pathwayChuk , Ikbkb , Ikbkg , Nfkb1 , Rela
adenine phoshoribosyltransferase deficiency pathwayTxn1
adenosine monophosphate deaminase deficiency pathwayTxn1
adenosine signaling pathwayChuk , Ikbkb , Map2k7 , Map3k1 , Nfkb1 , Prkcz
adenylosuccinate lyase deficiency pathwayTxn1
AICA-ribosuria pathwayTxn1
allograft rejection pathwayTnf
Alzheimer disease pathwayAdam17 , Casp8 , Fadd , Tnf , Tnfrsf1a
amyotrophic lateral sclerosis disease pathwayMap2k3 , Tnf , Tnfrsf1a , Tnfrsf1b
angiotensin II signaling pathwayPrkcz
antigen processing and presentation pathwayTnf
apoptotic cell death pathwayBirc2 , Birc3 , Casp8 , Chuk , Fadd , Ikbkb , Ikbkg , Nfkb1 , Rela , Ripk1 , Tnf , Tnfrsf1a , Tradd , Traf2
asthma disease pathwayTnf
azathioprine pharmacodynamics pathwayTxn1
B cell receptor signaling pathwayChuk , Ikbkb , Ikbkg , Nfkb1 , Rela
Bone morphogenetic proteins signaling pathwayMap3k7 , Tab1 , Tab2
c-Jun N-terminal kinases MAPK signaling pathwayMap2k7 , Map3k1 , Map3k3 , Map3k7 , Traf2
ceramide signaling pathwayBag4 , Birc3 , Casp8 , Chuk , Fadd , Ikbkb , Ikbkg , Madd , Map3k1 , Map4k4 , Nfkb1 , Nsmaf , Prkcz , Rela , Ripk1 , Smpd1 , Stat1 , Tnf , Tnfrsf1a , Tradd , Traf2
chemokine mediated signaling pathwayChuk , Ikbkb , Ikbkg , Nfkb1 , Prkcz , Rela , Stat1
chronic myeloid leukemia pathwayChuk , Ikbkb , Ikbkg , Nfkb1 , Rela
cytokine mediated signaling pathwayTnf , Tnfrsf1a , Tnfrsf1b
dilated cardiomyopathy pathwayTnf
eicosanoid signaling pathwayPrkcz
endocytosis pathwayCav1 , Itch , Prkci , Prkcz
Endoplasmic Reticulum-associated degradation pathwayMap2k7 , Traf2
Entamoeba histolyca infection pathwayNfkb1 , Rela , Tnf
ephrin - ephrin receptor bidirectional signaling axisMap3k7 , Map4k4
epidermal growth factor/neuregulin signaling pathwayAdam17 , Map2k7 , Prkcz , Stat1
Erk5 MAPK signaling pathwayMap3k3
erythropoietin signaling pathwayNfkb1 , Stat1
extrinsic apoptotic pathwayCasp8
FasL mediated signaling pathwayBirc2 , Birc3 , Casp8 , Chuk , Fadd , Ikbkb , Ikbkg , Map2k7 , Map3k1 , Ripk1 , Smpd1
Fc epsilon receptor mediated signaling pathwayMap2k3 , Map2k7 , Tnf
fibroblast growth factor signaling pathwayStat1
gonadotropin-releasing hormone signaling pathwayMap2k3 , Map2k7 , Map3k1 , Map3k3
graft-versus-host disease pathwayTnf
granulocyte-macrophage colony-stimulating factor signaling pathwayIkbkb , Stat1
hepatitis C virus infection pathwayChuk , Ikbkb , Ikbkg , Nfkb1 , Rela , Ripk1 , Stat1 , Tnf , Tnfrsf1a , Tradd , Traf2
Huntington disease pathwayCasp8
hypertrophic cardiomyopathy pathwayTnf
hypoxia inducible factor pathwayRack1
influenza A virus infection pathwayIkbkb , Map2k3 , Map2k7 , Nfkb1 , Rela , Stat1 , Tnf , Tnfrsf1a
insulin responsive facilitative sugar transporter mediated glucose transport pathwayPrkci , Prkcz
insulin signaling pathwayCav1 , Ikbkb , Prkci , Prkcz
insulin-like growth factor signaling pathwayPrkcz , Rack1
integrin mediated signaling pathwaySharpin
interleukin-1 signaling pathwayChuk , Ikbkb , Ikbkg , Map3k3 , Map3k7 , Nfkb1 , Prkci , Prkcz , Rela , Sqstm1 , Tab1 , Tab2 , Tab3
Interleukin-10 signaling pathwayStat1
interleukin-12 signaling pathwayMap2k3 , Nfkb1 , Rela , Stat1
interleukin-2 signaling pathwayStat1
interleukin-23 signaling pathwayNfkb1 , Rela , Stat1 , Tnf
interleukin-27 signaling pathwayStat1 , Tnf
interleukin-6 signaling pathwayAdam17 , Stat1
Jak-Stat signaling pathwayStat1
Kelley-Seegmiller syndrome pathwayTxn1
Leishmania infection pathwayMap3k7 , Nfkb1 , Rela , Stat1 , Tnf
Lesch-Nyhan syndrome pathwayTxn1
measles infection pathwayChuk , Map3k7 , Nfkb1 , Rack1 , Rela , Stat1
mercaptopurine pharmacodynamics pathwayTxn1
mitochondrial autophagy pathwaySqstm1
mitogen activated protein kinase signaling pathwayChuk , Ikbkb , Ikbkg , Map2k3 , Map2k7 , Map3k1 , Map3k3 , Map3k7 , Map4k2 , Map4k3 , Map4k4 , Nfkb1 , Rela , Tnf , Tnfrsf1a , Traf2
molybdenum cofactor deficiency pathwayTxn1
mTOR signaling pathwayIkbkb
Mycobacterium tuberculosis infection pathwayCasp8 , Fadd , Nfkb1 , Rela , Stat1 , Tnf , Tnfrsf1a , Tradd
myocarditis pathwayCasp8 , Cav1
neurotrophic factor signaling pathwayIkbkb , Map2k7 , Map3k1 , Map3k3 , Nfkb1 , Rela
NOD-like receptor signaling pathwayBirc2 , Birc3 , Casp8 , Chuk , Ikbkb , Ikbkg , Map3k7 , Nfkb1 , Rela , Tnf
Notch signaling pathwayAdam17 , Itch
nuclear factor kappa B signaling pathwayBirc2 , Chuk , Cyld , Ikbkb , Ikbkg , Map3k7 , Nfkb1 , Rbck1 , Rela , Rnf31 , Sharpin , Tab1 , Tab2 , Tab3 , Tnf , Tnfrsf1a
nuclear factor, erythroid 2 like 2 signaling pathwayIkbkb , Sqstm1
p38 MAPK signaling pathwayMap2k3 , Map3k1 , Map3k3 , Map3k5 , Map3k7 , Tab1 , Tab2 , Traf2 , Txn1
p53 signaling pathwayCasp8
pancreatic cancer pathwayChuk , Ikbkb , Ikbkg , Nfkb1 , Rela , Stat1
phosphatidylinositol 3-kinase-Akt signaling pathwayChuk , Map3k5
Plasmodium infection pathwayTnf
platelet-derived growth factor signaling pathwayCav1 , Map2k7 , Stat1
primary immunodeficiency disease pathwayIkbkg
prostate cancer pathwayChuk , Ikbkb , Ikbkg , Nfkb1 , Rela
protein kinase C (PKC) signaling pathwayPrkci , Prkcz , Rack1
purine metabolic pathwayTxn1
purine nucleoside phosphorylase deficiency pathwayTxn1
Reelin signaling pathwayMap2k7
Retinoic acid-inducible gene (RIG) I-like receptor signaling pathwayCasp8 , Chuk , Cyld , Fadd , Ikbkb , Ikbkg , Map3k1 , Map3k7 , Nfkb1 , Rela , Ripk1 , Tnf , Tradd , Traf2
reverse cholesterol transport pathwayCav1
rheumatoid arthritis disease pathwayTnf
ribosome biogenesis pathwayRack1
small cell lung cancer pathwayBirc2 , Birc3 , Chuk , Ikbkb , Ikbkg , Nfkb1 , Rela , Traf2
sphingolipid metabolic pathwaySmpd1 , Smpd2
syndecan signaling pathwayRack1
systemic lupus erythematosus pathwayTnf
T cell receptor signaling pathwayChuk , Ikbkb , Ikbkg , Map2k7 , Map3k7 , Nfkb1 , Rela , Tnf
the extracellular signal-regulated Raf/Mek/Erk signaling pathwayMap3k1
tioguanine pharmacodynamics pathwayTxn1
titanium dioxide nanoparticle response pathwayCasp8
Toll-like receptor signaling pathwayCasp8 , Chuk , Fadd , Ikbkb , Ikbkg , Map2k3 , Map2k7 , Map3k7 , Nfkb1 , Rela , Ripk1 , Stat1 , Tab1 , Tab2 , Tab3 , Tnf , Tradd
Toxoplasma gondii infection pathwayBirc2 , Birc3 , Casp8 , Chuk , Ikbkb , Ikbkg , Map2k3 , Map3k7 , Nfkb1 , Rela , Stat1 , Tnf , Tnfrsf1a
Trail mediated signaling pathwayCasp8 , Chuk , Fadd , Ikbkb , Ikbkg , Map3k1 , Ripk1 , Smpd1 , Tradd , Traf2
transforming growth factor-beta Smad dependent signaling pathwayCav1 , Itch , Map3k7 , Tab1 , Tab2
transforming growth factor-beta superfamily mediated signaling pathwayTnf
Trypanosoma brucei infection pathwayTnf
Trypanosoma cruzi infection pathwayCasp8 , Chuk , Fadd , Ikbkb , Ikbkg , Nfkb1 , Rela , Tnf , Tnfrsf1a
tumor necrosis factor mediated signaling pathwayAdam17 , Bag4 , Birc2 , Birc3 , Casp8 , Cav1 , Chuk , Cyld , Fadd , Ikbkb , Ikbkg , Itch , Madd , Map2k3 , Map2k7 , Map3k1 , Map3k3 , Map3k5 , Map3k7 , Map4k2 , Map4k3 , Map4k4 , Map4k5 , Nfkb1 , Nrk , Nsmaf , Prkci , Prkcz , Rack1 , Rbck1 , Rela , Rffl , Ripk1 , Rnf11 , Rnf31 , Sharpin , Smpd1 , Smpd2 , Sqstm1 , Stat1 , Tab1 , Tab2 , Tab3 , Tax1bp1 , Tnf , Tnfaip3 , Tnfrsf1a , Tnfrsf1b , Tnik , Tradd , Traf2 , Txn1
type 1 diabetes mellitus pathwayTnf
type 2 diabetes mellitus pathwayIkbkb , Prkcz , Tnf
type II interferon signaling pathwayMap3k1 , Stat1
ubiquitin/proteasome degradation pathwayBirc2 , Birc3 , Itch , Map3k1
vascular endothelial growth factor signaling pathwayCav1 , Map2k3 , Prkcz
Wnt signaling pathwayMap3k7
Wnt signaling, canonical pathwayCav1
Wnt signaling, non-canonical pathwayMap3k7 , Prkcz , Tab1 , Tab2
xanthinuria disease pathwayTxn1
xanthinuria disease pathway, type ITxn1
xanthinuria disease pathway, type IITxn1
Phenotype Annotations Associated with Genes in the tumor necrosis factor mediated signaling pathway

References Associated with the tumor necrosis factor mediated signaling pathway:

Ontology Path Diagram:

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Import into Pathway Studio: