KEGG   PATHWAY: hai04064
Entry
hai04064                    Pathway                                
Name
NF-kappa B signaling pathway - Hipposideros armiger (great roundleaf bat)
Description
Nuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are several pathways leading to NF-kappa B-activation. The canonical pathway is induced by tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or byproducts of bacterial and viral infections. This pathway relies on IKK- mediated IkappaB-alpha phosphorylation on Ser32 and 36, leading to its degradation, which allows the p50/p65 NF-kappa B dimer to enter the nucleus and activate gene transcription. Atypical pathways are IKK-independent and rely on phosphorylation of IkappaB-alpha on Tyr42 or on Ser residues in IkappaB-alpha PEST domain. The non-canonical pathway is triggered by particular members of the TNFR superfamily, such as lymphotoxin-beta (LT-beta) or BAFF. It involves NIK and IKK-alpha-mediated p100 phosphorylation and processing to p52, resulting in nuclear translocation of p52/RelB heterodimers.
Class
Environmental Information Processing; Signal transduction
Pathway map
hai04064  NF-kappa B signaling pathway
hai04064

Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109378262  uncharacterized protein LOC109378262 [KO:K10785]
109390746  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
109390751  tyrosine-protein kinase Lck-like [KO:K05856] [EC:2.7.10.2]
109391988  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
109385909  LAT; linker for activation of T-cells family member 1 [KO:K07362]
109379925  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
109383803  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
109375897  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
109394449  LYN; tyrosine-protein kinase Lyn [KO:K05854] [EC:2.7.10.2]
109380942  BLNK; B-cell linker protein isoform X1 [KO:K07371]
109374529  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
109391632  TIMM29; uncharacterized protein C19orf52 homolog isoform X1 [KO:K07370] [EC:2.7.10.2]
109378365  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
109386578  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109394512  CARD10; caspase recruitment domain-containing protein 10 isoform X1 [KO:K20912]
109380126  CARD11; caspase recruitment domain-containing protein 11 isoform X1 [KO:K07367]
109383660  CARD14; caspase recruitment domain-containing protein 14 isoform X1 [KO:K20913]
109372895  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
109381749  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
109393524  IL1B; interleukin-1 beta isoform X1 [KO:K04519]
109395478  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
109393491  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
109394352  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
109388403  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
109381153  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
109373073  TNF; tumor necrosis factor isoform X1 [KO:K03156]
109373644  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
109396595  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
109390108  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
109381672  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
109379157  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
109375115  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
109375125  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
109376360  LOW QUALITY PROTEIN: putative inhibitor of apoptosis [KO:K16060]
109385584  EDA; ectodysplasin-A isoform X1 [KO:K05480]
109394044  EDAR; tumor necrosis factor receptor superfamily member EDAR isoform X1 [KO:K05162]
109387704  EDARADD; ectodysplasin-A receptor-associated adapter protein isoform X1 [KO:K23324]
109383313  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
109385566  EDA2R; tumor necrosis factor receptor superfamily member 27 [KO:K05163]
109371521  DDX58; probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:5.6.2.6]
109379737  TRIM25; E3 ubiquitin/ISG15 ligase TRIM25 [KO:K10652] [EC:2.3.2.27]
109372124  LBP; lipopolysaccharide-binding protein [KO:K05399]
109393398  CD14; monocyte differentiation antigen CD14 [KO:K04391]
109385740  TLR4; toll-like receptor 4 [KO:K10160]
109383283  LY96; lymphocyte antigen 96 [KO:K05400]
109391405  TIRAP; toll/interleukin-1 receptor domain-containing adapter protein isoform X1 [KO:K05403]
109387401  TIR domain-containing adapter molecule 2-like [KO:K05409]
109388568  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
109396161  CD40LG; CD40 ligand [KO:K03161]
109379888  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
109381072  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
109386844  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
109390774  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
109373061  LTA; lymphotoxin-alpha [KO:K05468]
109373072  LTB; lymphotoxin-beta isoform X1 [KO:K03157]
109373672  LTBR; tumor necrosis factor receptor superfamily member 3 isoform X1 [KO:K03159]
109395015  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
109389465  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
109392251  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
109380888  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
109374428  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
109393334  TNFSF13B; tumor necrosis factor ligand superfamily member 13B isoform X1 [KO:K05476]
109377512  TNFRSF13C; tumor necrosis factor receptor superfamily member 13C isoform X1 [KO:K05151]
109377344  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
109379632  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
109386279  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
109391470  PARP1; poly [ADP-ribose] polymerase 1 isoform X1 [KO:K24070] [EC:2.4.2.30]
109388654  PIAS4; E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:2.3.2.27]
109385966  UBE2I; SUMO-conjugating enzyme UBC9 [KO:K10577]
109371552  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
109375647  PIDD1; p53-induced death domain-containing protein 1 [KO:K10130]
109388966  ERC1; ELKS/Rab6-interacting/CAST family member 1 [KO:K16072]
109383860  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109372541  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109384322  RELA; transcription factor p65 isoform X1 [KO:K04735]
109374732  PPP1R13L; relA-associated inhibitor isoform X1 [KO:K27356]
109379239  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
109390892  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
109384429  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
109373362  bcl-2-like protein 1 isoform X1 [KO:K04570]
109390784  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
109384926  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109374090  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
109390584  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109385737  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
109381387  bcl-2-related protein A1-like [KO:K02162]
109379582  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
109394819  CXCL8; interleukin-8 [KO:K10030]
109385645  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
109379092  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
109379751  C-C motif chemokine 4 [KO:K12964]
109371836  growth-regulated protein homolog gamma-like [KO:K05505]
109394813  growth-regulated protein homolog gamma-like [KO:K05505]
109371834  growth-regulated protein homolog gamma-like [KO:K05505]
109371359  VCAM1; vascular cell adhesion protein 1 isoform X1 [KO:K06527]
109371644  PLAU; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
109394423  CSNK2A2; casein kinase II subunit alpha' [KO:K03097] [EC:2.7.11.1]
109384437  CSNK2A1; casein kinase II subunit alpha isoform X1 [KO:K03097] [EC:2.7.11.1]
109373126  CSNK2B; casein kinase II subunit beta [KO:K03115]
109372771  RELB; transcription factor RelB [KO:K09253]
109374976  C-C motif chemokine 13-like [KO:K16595]
109371763  C-C motif chemokine 21-like isoform X1 [KO:K16062]
109395869  CXCL12; stromal cell-derived factor 1 isoform X1 [KO:K10031]
109391654  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:21772278
  Authors
Oeckinghaus A, Hayden MS, Ghosh S
  Title
Crosstalk in NF-kappaB signaling pathways.
  Journal
Nat Immunol 12:695-708 (2011)
DOI:10.1038/ni.2065
Reference
PMID:19203223
  Authors
Gloire G, Piette J
  Title
Redox regulation of nuclear post-translational modifications during NF-kappaB activation.
  Journal
Antioxid Redox Signal 11:2209-22 (2009)
DOI:10.1089/ARS.2009.2463
Reference
PMID:17183360
  Authors
Perkins ND
  Title
Integrating cell-signalling pathways with NF-kappaB and IKK function.
  Journal
Nat Rev Mol Cell Biol 8:49-62 (2007)
DOI:10.1038/nrm2083
Reference
PMID:16264088
  Authors
Lindstrom TM, Bennett PR
  Title
The role of nuclear factor kappa B in human labour.
  Journal
Reproduction 130:569-81 (2005)
DOI:10.1530/rep.1.00197
Reference
PMID:22017430
  Authors
Razani B, Reichardt AD, Cheng G
  Title
Non-canonical NF-kappaB signaling activation and regulation: principles and perspectives.
  Journal
Immunol Rev 244:44-54 (2011)
DOI:10.1111/j.1600-065X.2011.01059.x
Reference
PMID:21173796
  Authors
Sun SC
  Title
Non-canonical NF-kappaB signaling pathway.
  Journal
Cell Res 21:71-85 (2011)
DOI:10.1038/cr.2010.177
Reference
PMID:17431096
  Authors
Neumann M, Naumann M
  Title
Beyond IkappaBs: alternative regulation of NF-kappaB activity.
  Journal
FASEB J 21:2642-54 (2007)
DOI:10.1096/fj.06-7615rev
Reference
PMID:22119011
  Authors
Verhelst K, Carpentier I, Beyaert R
  Title
Regulation of TNF-induced NF-kappaB activation by different cytoplasmic ubiquitination events.
  Journal
Cytokine Growth Factor Rev 22:277-86 (2011)
DOI:10.1016/j.cytogfr.2011.11.002
Reference
PMID:22017435
  Authors
Rickert RC, Jellusova J, Miletic AV
  Title
Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease.
  Journal
Immunol Rev 244:115-33 (2011)
DOI:10.1111/j.1600-065X.2011.01067.x
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:16984817
  Authors
Grivennikov SI, Kuprash DV, Liu ZG, Nedospasov SA
  Title
Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: From simple paradigms to complex mechanisms.
  Journal
Int Rev Cytol 252:129-61 (2006)
DOI:10.1016/S0074-7696(06)52002-9
Reference
PMID:16356770
  Authors
Wada T, Nakashima T, Hiroshi N, Penninger JM
  Title
RANKL-RANK signaling in osteoclastogenesis and bone disease.
  Journal
Trends Mol Med 12:17-25 (2006)
DOI:10.1016/j.molmed.2005.11.007
Reference
PMID:17098202
  Authors
Schulze-Luehrmann J, Ghosh S
  Title
Antigen-receptor signaling to nuclear factor kappa B.
  Journal
Immunity 25:701-15 (2006)
DOI:10.1016/j.immuni.2006.10.010
Reference
PMID:15134788
  Authors
Weil R, Israel A
  Title
T-cell-receptor- and B-cell-receptor-mediated activation of NF-kappaB in lymphocytes.
  Journal
Curr Opin Immunol 16:374-81 (2004)
DOI:10.1016/j.coi.2004.03.003
Reference
PMID:15905862
  Authors
Siebenlist U, Brown K, Claudio E
  Title
Control of lymphocyte development by nuclear factor-kappaB.
  Journal
Nat Rev Immunol 5:435-45 (2005)
DOI:10.1038/nri1629
Reference
PMID:14657271
  Authors
Lucas PC, McAllister-Lucas LM, Nunez G
  Title
NF-kappaB signaling in lymphocytes: a new cast of characters.
  Journal
J Cell Sci 117:31-9 (2004)
DOI:10.1242/jcs.00904
Reference
PMID:19726767
  Authors
Khan WN
  Title
B cell receptor and BAFF receptor signaling regulation of B cell homeostasis.
  Journal
J Immunol 183:3561-7 (2009)
DOI:10.4049/jimmunol.0800933
Reference
PMID:19302050
  Authors
Vallabhapurapu S, Karin M
  Title
Regulation and function of NF-kappaB transcription factors in the immune system.
  Journal
Annu Rev Immunol 27:693-733 (2009)
DOI:10.1146/annurev.immunol.021908.132641
Reference
PMID:17047224
  Authors
Hacker H, Karin M
  Title
Regulation and function of IKK and IKK-related kinases.
  Journal
Sci STKE 2006:re13 (2006)
DOI:10.1126/stke.3572006re13
Reference
PMID:21872579
  Authors
Sabatel H, Pirlot C, Piette J, Habraken Y
  Title
Importance of PIKKs in NF-kappaB activation by genotoxic stress.
  Journal
Biochem Pharmacol 82:1371-83 (2011)
DOI:10.1016/j.bcp.2011.07.105
Reference
PMID:21187855
  Authors
Miyamoto S
  Title
Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage.
  Journal
Cell Res 21:116-30 (2011)
DOI:10.1038/cr.2010.179
Reference
PMID:18832076
  Authors
Brzoska K, Szumiel I
  Title
Signalling loops and linear pathways: NF-kappaB activation in response to genotoxic stress.
  Journal
Mutagenesis 24:1-8 (2009)
DOI:10.1093/mutage/gen056
Reference
PMID:17607554
  Authors
Wu ZH, Miyamoto S
  Title
Many faces of NF-kappaB signaling induced by genotoxic stress.
  Journal
J Mol Med (Berl) 85:1187-202 (2007)
DOI:10.1007/s00109-007-0227-9
Reference
PMID:22390971
  Authors
Maelfait J, Beyaert R
  Title
Emerging role of ubiquitination in antiviral RIG-I signaling.
  Journal
Microbiol Mol Biol Rev 76:33-45 (2012)
DOI:10.1128/MMBR.05012-11
Reference
PMID:18613837
  Authors
Ware CF
  Title
Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways.
  Journal
Immunol Rev 223:186-201 (2008)
DOI:10.1111/j.1600-065X.2008.00629.x
Reference
PMID:15546385
  Authors
Schneider K, Potter KG, Ware CF
  Title
Lymphotoxin and LIGHT signaling pathways and target genes.
  Journal
Immunol Rev 202:49-66 (2004)
DOI:10.1111/j.0105-2896.2004.00206.x
Reference
PMID:22152226
  Authors
Remouchamps C, Boutaffala L, Ganeff C, Dejardin E
  Title
Biology and signal transduction pathways of the Lymphotoxin-alphabeta/LTbetaR system.
  Journal
Cytokine Growth Factor Rev 22:301-10 (2011)
DOI:10.1016/j.cytogfr.2011.11.007
Reference
PMID:21135871
  Authors
Liu S, Chen ZJ
  Title
Expanding role of ubiquitination in NF-kappaB signaling.
  Journal
Cell Res 21:6-21 (2011)
DOI:10.1038/cr.2010.170
Reference
PMID:19489733
  Authors
Skaug B, Jiang X, Chen ZJ
  Title
The role of ubiquitin in NF-kappaB regulatory pathways.
  Journal
Annu Rev Biochem 78:769-96 (2009)
DOI:10.1146/annurev.biochem.78.070907.102750
Reference
PMID:20300215
  Authors
Wertz IE, Dixit VM
  Title
Signaling to NF-kappaB: regulation by ubiquitination.
  Journal
Cold Spring Harb Perspect Biol 2:a003350 (2010)
DOI:10.1101/cshperspect.a003350
Reference
PMID:11875461
  Authors
Karin M, Lin A
  Title
NF-kappaB at the crossroads of life and death.
  Journal
Nat Immunol 3:221-7 (2002)
DOI:10.1038/ni0302-221
Reference
PMID:12654254
  Authors
Lin A, Karin M
  Title
NF-kappaB in cancer: a marked target.
  Journal
Semin Cancer Biol 13:107-14 (2003)
DOI:10.1016/S1044-579X(02)00128-1
Reference
PMID:16251197
  Authors
Morlon A, Munnich A, Smahi A
  Title
TAB2, TRAF6 and TAK1 are involved in NF-kappaB activation induced by the TNF-receptor, Edar and its adaptator Edaradd.
  Journal
Hum Mol Genet 14:3751-7 (2005)
DOI:10.1093/hmg/ddi405
Reference
PMID:24070496
  Authors
Sadier A, Viriot L, Pantalacci S, Laudet V
  Title
The ectodysplasin pathway: from diseases to adaptations.
  Journal
Trends Genet 30:24-31 (2014)
DOI:10.1016/j.tig.2013.08.006
Reference
PMID:26260321
  Authors
Verhelst K, Gardam S, Borghi A, Kreike M, Carpentier I, Beyaert R
  Title
XEDAR activates the non-canonical NF-kappaB pathway.
  Journal
Biochem Biophys Res Commun 465:275-80 (2015)
DOI:10.1016/j.bbrc.2015.08.019
Reference
PMID:27508514
  Authors
McDaniel DK, Eden K, Ringel VM, Allen IC
  Title
Emerging Roles for Noncanonical NF-kappaB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology.
  Journal
Inflamm Bowel Dis 22:2265-79 (2016)
DOI:10.1097/MIB.0000000000000858
Reference
PMID:12787560
  Authors
Mikkola ML, Thesleff I
  Title
Ectodysplasin signaling in development.
  Journal
Cytokine Growth Factor Rev 14:211-24 (2003)
DOI:10.1016/S1359-6101(03)00020-0
Reference
PMID:26646590
  Authors
Hu Y, Ge W, Wang X, Sutendra G, Zhao K, Dedeic Z, Slee EA, Baer C, Lu X
  Title
Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-kappaB.
  Journal
Oncotarget 6:42478-90 (2015)
DOI:10.18632/oncotarget.6478
Related
pathway
hai03050  Proteasome
hai04020  Calcium signaling pathway
hai04060  Cytokine-cytokine receptor interaction
hai04120  Ubiquitin mediated proteolysis
hai04210  Apoptosis
hai04380  Osteoclast differentiation
hai04620  Toll-like receptor signaling pathway
hai04622  RIG-I-like receptor signaling pathway
hai04660  T cell receptor signaling pathway
hai04662  B cell receptor signaling pathway
KO pathway
ko04064   
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