KEGG   PATHWAY: psiu04668
Entry
psiu04668                   Pathway                                
Name
TNF signaling pathway - Phocoena sinus (vaquita)
Description
Tumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF is assembled to a homotrimer and binds to its receptors (TNFR1, TNFR2) resulting in the trimerization of TNFR1 or TNFR2. TNFR1 is expressed by nearly all cells and is the major receptor for TNF (also called TNF-alpha). In contrast, TNFR2 is expressed in limited cells such as CD4 and CD8 T lymphocytes, endothelial cells, microglia, oligodendrocytes, neuron subtypes, cardiac myocytes, thymocytes and human mesenchymal stem cells. It is the receptor for both TNF and LTA (also called TNF-beta). Upon binding of the ligand, TNFR mediates the association of some adaptor proteins such as TRADD or TRAF2, which in turn initiate recruitment of signal transducers. TNFR1 signaling induces activation of many genes, primarily controlled by two distinct pathways, NF-kappa B pathway and the MAPK cascade, or apoptosis and necroptosis. TNFR2 signaling activates NF-kappa B pathway including PI3K-dependent NF-kappa B pathway and JNK pathway leading to survival.
Class
Environmental Information Processing; Signal transduction
Pathway map
psiu04668  TNF signaling pathway
psiu04668

Other DBs
GO: 0033209
Organism
Phocoena sinus (vaquita) [GN:psiu]
Gene
116762489  TNF; tumor necrosis factor [KO:K03156]
116760562  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
116746683  BAG4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558]
116763969  ADAM17; LOW QUALITY PROTEIN: disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
116739964  RHBDF1; inactive rhomboid protein 1 isoform X1 [KO:K27588]
116745395  RHBDF2; LOW QUALITY PROTEIN: inactive rhomboid protein 2 [KO:K27588]
116758456  FRMD8; FERM domain-containing protein 8 isoform X1 [KO:K23972]
116755387  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
116738804  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
116762851  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
116757989  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
116758079  BIRC2; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2 [KO:K16060]
116763242  MAP3K7; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
116760244  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
116763460  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
116747683  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
116745732  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
116753033  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
116750630  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
116754735  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116741257  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116751302  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116761115  JUN; transcription factor AP-1 [KO:K04448]
116749519  FOS; proto-oncogene c-Fos [KO:K04379]
116740798  ITCH; E3 ubiquitin-protein ligase Itchy homolog isoform X1 [KO:K05632] [EC:2.3.2.26]
116756986  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
116745655  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
116746300  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
116760605  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
116760782  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
116762796  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
116762798  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116739921  CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048]
116763459  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
116745052  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
116747398  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
116746707  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
116741676  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
116749797  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
116758150  RELA; transcription factor p65 isoform X1 [KO:K04735]
116754222  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116748892  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
116747589  MAP2K1; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116738910  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116740620  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
116748377  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
116757345  RPS6KA4; ribosomal protein S6 kinase alpha-4 isoform X1 [KO:K16510] [EC:2.7.11.1]
116756730  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
116755320  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
116740243  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
116758621  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
116751955  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
116759300  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
116756632  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
116761029  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
116759616  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
116762930  ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
116757390  FADD; FAS-associated death domain protein [KO:K02373]
116757029  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
116756541  CASP10; caspase-10 isoform X1 [KO:K04400] [EC:3.4.22.63]
116742039  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
116746660  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
116744759  MLKL; LOW QUALITY PROTEIN: mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
116765201  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial [KO:K15637] [EC:3.1.3.16]
116761342  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
116743628  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
116747379  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
116744937  C-C motif chemokine 2 [KO:K14624]
116745948  CCL5; C-C motif chemokine 5 [KO:K12499]
116757007  CCL20; C-C motif chemokine 20 isoform X1 [KO:K14625]
116753842  growth-regulated alpha protein-like [KO:K05505]
116754232  growth-regulated alpha protein-like [KO:K05505]
116754241  growth-regulated alpha protein [KO:K05505]
116753815  C-X-C motif chemokine 6-like [KO:K05506]
116754435  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
116744478  CX3CL1; fractalkine [KO:K05508]
116756768  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
116751328  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
116741753  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
116763870  IL18R1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
116740302  JAG1; protein jagged-1 isoform X1 [KO:K06052]
116764546  IL1B; interleukin-1 beta [KO:K04519]
116759822  IL6; interleukin-6 isoform X1 [KO:K05405]
116754772  IL15; interleukin-15 isoform X1 [KO:K05433]
116739256  LIF; leukemia inhibitory factor isoform X1 [KO:K05419]
116762490  LTA; lymphotoxin-alpha [KO:K05468]
116744388  BCL3; B-cell lymphoma 3 protein [KO:K09258]
116746400  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
116763624  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
116755406  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
116751774  T-cell-specific guanine nucleotide triphosphate-binding protein 2-like [KO:K17072]
116752077  JUNB; transcription factor jun-B [KO:K09028]
116758766  stromelysin-1-like [KO:K01394] [EC:3.4.24.17]
116740660  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
116748985  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
116762788  EDN1; endothelin-1 isoform X1 [KO:K16366]
116746676  VEGFC; vascular endothelial growth factor C [KO:K05449]
116747916  VEGFD; vascular endothelial growth factor D [KO:K05449]
116743980  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
116751656  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
116761340  SELE; E-selectin isoform X1 [KO:K06494]
116744736  VCAM1; vascular cell adhesion protein 1 [KO:K06527]
116742225  LOW QUALITY PROTEIN: vascular cell adhesion protein 1-like [KO:K06527]
116759534  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
116756594  TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141]
116748433  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
116752953  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116752990  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
116751286  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116750604  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116742613  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
116751944  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116743673  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116759669  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116748950  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116756065  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
116752290  IRF1; interferon regulatory factor 1 [KO:K09444]
116755914  IFNB1; interferon beta [KO:K05415]
Reference
PMID:23085193
  Authors
Chu WM
  Title
Tumor necrosis factor.
  Journal
Cancer Lett 328:222-5 (2013)
DOI:10.1016/j.canlet.2012.10.014
Reference
PMID:23531747
  Authors
Shuh M, Bohorquez H, Loss GE Jr, Cohen AJ
  Title
Tumor Necrosis Factor-alpha: Life and Death of Hepatocytes During Liver Ischemia/Reperfusion Injury.
  Journal
Ochsner J 13:119-30 (2013)
Reference
PMID:11897488
  Authors
MacEwan DJ
  Title
TNF receptor subtype signalling: differences and cellular consequences.
  Journal
Cell Signal 14:477-92 (2002)
DOI:10.1016/S0898-6568(01)00262-5
Reference
PMID:22296764
  Authors
Newton K, Dixit VM
  Title
Signaling in innate immunity and inflammation.
  Journal
Cold Spring Harb Perspect Biol 4:a006049 (2012)
DOI:10.1101/cshperspect.a006049
Reference
PMID:10581243
  Authors
Pomerantz JL, Baltimore D
  Title
NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase.
  Journal
EMBO J 18:6694-704 (1999)
DOI:10.1093/emboj/18.23.6694
Reference
PMID:21232019
  Authors
Naude PJ, den Boer JA, Luiten PG, Eisel UL
  Title
Tumor necrosis factor receptor cross-talk.
  Journal
FEBS J 278:888-98 (2011)
DOI:10.1111/j.1742-4658.2011.08017.x
Reference
PMID:20489699
  Authors
Faustman D, Davis M
  Title
TNF receptor 2 pathway: drug target for autoimmune diseases.
  Journal
Nat Rev Drug Discov 9:482-93 (2010)
DOI:10.1038/nrd3030
Reference
PMID:14532286
  Authors
Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, Appel M, Orenstein J, Moss B, Lenardo MJ
  Title
A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.
  Journal
J Biol Chem 278:51613-21 (2003)
DOI:10.1074/jbc.M305633200
Reference
PMID:26869525
  Authors
Lee MY, Nam KH, Choi KC
  Title
iRhoms; Its Functions and Essential Roles.
  Journal
Biomol Ther (Seoul) 24:109-14 (2016)
DOI:10.4062/biomolther.2015.149
Related
pathway
psiu04010  MAPK signaling pathway
psiu04064  NF-kappa B signaling pathway
psiu04120  Ubiquitin mediated proteolysis
psiu04151  PI3K-Akt signaling pathway
psiu04210  Apoptosis
KO pathway
ko04668   
LinkDB

DBGET integrated database retrieval system